Publications by authors named "Dongyan Cao"

108 Publications

Non-open-heart surgery for intravascular leiomyomatosis extending from the inferior vena cava to the right heart chamber.

J Vasc Surg Venous Lymphat Disord 2021 Jul 9. Epub 2021 Jul 9.

Department of Gynecology and Obstetrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Objective: In the present study, we analyzed the advantages and feasibility of non-open-heart surgery without cardiopulmonary bypass for intracardiac intravenous leiomyomatosis.

Methods: We retrospectively reviewed 23 cases of intracardiac intravenous leiomyomatosis and divided them into a noncardiopulmonary bypass (NCPB) group (9 cases) and a cardiopulmonary bypass (CPB) group (14 cases) according to the surgical treatment received. The clinical characteristics and anatomic features, including the diameter of the tumor, right atrium, and inferior vena cava, were recorded, and the perioperative data, including the operation time, blood loss, postoperative hemoglobin change, and follow-up results, were analyzed and compared between the two groups.

Results: The NCPB group had required a shorter operation time (321.9 ± 104.2 minutes vs 526.3 ± 95.6 minutes; P < .001) and had experienced less blood loss (456.3 ± 249.9 mL vs 815.4 ± 435.6 mL; P = .048) compared with the CPB group. The NCPB group had a small maximum cross-sectional area of the tumor inside the right atrium (475.5 ± 509.6 mm), a low proportion of the maximum cross-sectional area of the entrance of the right atrium (average, 26.1%), no tricuspid valve or atrial wall involvement, and high mobility inside the inferior vena cava and heart chamber. All 23 patients had recovered well postoperatively, and no recurrence had developed during 24 months of follow-up.

Conclusions: For intravenous leiomyomatosis with a smaller cross-sectional area in the right atrium that can be mobilized, surgery without CBP is feasible and should be considered.
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http://dx.doi.org/10.1016/j.jvsv.2021.06.016DOI Listing
July 2021

Single-cell RNA-sequencing atlas reveals an MDK-dependent immunosuppressive environment in ErbB pathway-mutated gallbladder cancer.

J Hepatol 2021 Jun 22. Epub 2021 Jun 22.

Department of Gastroenterology Surgery, Songjiang Central Hospital Affiliated to The First People's Hospital of Shanghai Jiao Tong University, Shanghai, 201600, China.

Background & Aims: Our previous genomic whole-exome sequencing (WES) data identified the key ErbB pathway mutations that play an essential role in regulating the malignancy of gallbladder cancer (GBC). Here, we tested the hypothesis that individual cellular components of the tumor microenvironment (TME) in GBC function differentially to participate in ErbB pathway mutation-dependent tumor progression.

Methods: We engaged single-cell RNA sequencing to reveal transcriptomic heterogeneity and intercellular crosstalk from 13 human GBC and adjacent normal tissues. In addition, we performed WES analysis to reveal the genomic variations related to tumor malignancy. A variety of bulk RNA sequencing, immunohistochemical staining, immunofluorescence staining and functional experiments were employed to study the difference between ErbB pathway mutation and non-mutation tissues.

Results: We identified sixteen cell types from a total of 114,927 cells, in which epithelial cells, M2 macrophages, and Treg were predominant in ErbB pathway mutation tumors. Furthermore, epithelial cell subtype 1, 2 and 3 were mainly found in the adenocarcinoma and subtype 4 was present in adenosquamous carcinoma. The ErbB pathway mutation tumors harbored larger populations of epithelial cell subtype 1 and 2, and expressed higher levels of secreted midkine (MDK) than non-ErbB pathway mutation tumors. Increased MDK resulted in interaction with its receptor LRP1 expressed by tumor infiltrating macrophages and promoted immuno-suppressive macrophage differentiation. Moreover, the crosstalk between macrophage-secreted CXCL10 and its receptor CXCR3 on Tregs was induced in GBC with ErbB pathway mutations. Elevated MDK was correlated with poor overall survival of GBC patients.

Conclusions: This study has provided valuable insights into transcriptomic heterogeneity and the global cellular network in the TME, which coordinately functions to promote the progression of GBC with ErbB pathway mutations; thus unveiling novel cellular and molecular targets for cancer therapy.

Lay Summary: We employed single-cell RNA sequencing and functional assays to reveal transcriptomic heterogeneity and intercellular crosstalk in GBC patients. GBC cancers were characterized with heterogenic cellular ecosystem in which the ErbB pathway mutations were associated with anti-cancer immunity and cancer development. Increased MDK from cancer cells of ErbB pathway mutation tumors resulted in interaction with its receptor LRP1 expressed by tumor infiltrating macrophages and promoted immuno-suppressive macrophage differentiation. In addition, the crosstalk between macrophage-secreted CXCL10 and its receptor CXCR3 on Tregs was induced in GBC with ErbB pathway mutations, which contributes to GBC progression.
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http://dx.doi.org/10.1016/j.jhep.2021.06.023DOI Listing
June 2021

Analysis of the genomic landscape of yolk sac tumors reveals mechanisms of evolution and chemoresistance.

Nat Commun 2021 06 11;12(1):3579. Epub 2021 Jun 11.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Yolk sac tumors (YSTs) are a major histological subtype of malignant ovarian germ cell tumors with a relatively poor prognosis. The molecular basis of this disease has not been thoroughly characterized at the genomic level. Here we perform whole-exome and RNA sequencing on 41 clinical tumor samples from 30 YST patients, with distinct responses to cisplatin-based chemotherapy. We show that microsatellite instability status and mutational signatures are informative of chemoresistance. We identify somatic driver candidates, including significantly mutated genes KRAS and KIT and copy-number alteration drivers, including deleted ARID1A and PARK2, and amplified ZNF217, CDKN1B, and KRAS. YSTs have very infrequent TP53 mutations, whereas the tumors from patients with abnormal gonadal development contain both KRAS and TP53 mutations. We further reveal a role of OVOL2 overexpression in YST resistance to cisplatin. This study lays a critical foundation for understanding key molecular aberrations in YSTs and developing related therapeutic strategies.
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http://dx.doi.org/10.1038/s41467-021-23681-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196104PMC
June 2021

Tumor Volume Predicts High-Risk Patients and Guides Initial Chemoradiotherapy for Early Cervical Cancer.

Front Oncol 2021 27;11:640846. Epub 2021 Apr 27.

Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

We evaluated the relationship between the minimum tumor-free margin, tumor volume, and adverse pathological risk factors in early cervical cancer and explored the predictive value of these parameters for different types of risk patients to guide individualized therapeutic strategies. Patients who received the initial treatment of radical operation of cervical cancer and their postoperative pathological reports in our hospital from July 1, 2017, to June 30, 2019, were reviewed. Their minimum tumor-free margin and tumor volume were measured on preoperative magnetic resonance imaging. Student's t-test and the receiver operating characteristic curve analysis were used for data analysis. A total of 240 patients were included. Adverse pathological risk factors were as follows: deep cervical infiltration, 95 (39.6%) cases; lymph vascular space invasion, 91 (37.9%); lymph node metastasis, 20 (8.3%); parametrial infiltration, 8 (3.3%); tumor diameter ≥4 cm, 7 (2.9%); and positive surgical margin, 1 (0.4%). According to the adverse pathological factors, there were 20 (8.3%) high-risk patients, 50 (20.8%) medium-risk patients, and 170 (70.8%) low-risk patients. The ranges of the minimum tumor-free margin and tumor volume were 0.01-13.5 mm and 105-27,990 mm, respectively. The minimum tumor-free margin with lymph node metastasis was significantly smaller than that without (P <0.05). The tumor volume with parametrial infiltration, deep cervical infiltration, or lymph vascular space invasion was significantly greater than that without (P < 0.05). The tumor volume was significantly different among low-, medium-, and high-risk patients (P <0.05). Tumor volume was of predictive value for high-risk patients (P < 0.05). With 3,505 mm as the cutoff value, the sensitivity and specificity for the prediction of high-risk patients were 88.9% and 84.8%, respectively. Tumor volume can be used as a great predictor of high-risk patients (cutoff value, 3,505 mm), which could be an indication of initial chemoradiotherapy for early cervical cancer.
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http://dx.doi.org/10.3389/fonc.2021.640846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111085PMC
April 2021

SIRT3 inhibits gallbladder cancer by induction of AKT-dependent ferroptosis and blockade of epithelial-mesenchymal transition.

Cancer Lett 2021 Jul 16;510:93-104. Epub 2021 Apr 16.

Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 200127, China; Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai, 200127, China; Shanghai Research Center of Biliary Tract Disease, Shanghai, 200092, China. Electronic address:

Dysfunction of Sirtuin 3 (SIRT3), an NAD-dependent histone deacetylase, impairs varied mitochondrial metabolic pathways in human cancer. Here, we explored suppressive activity of SIRT3 in the progression of gallbladder cancer (GBC). Expression levels of SIRT3 in patients with GBC were lower than those in the adjacent normal tissue. In addition, decreased expression of SIRT3 in these patients was correlated with poor overall survival. Knockdown of SIRT3 gene in GBC cell lines induced mitochondrial respiration and energy metabolism, but inhibited oxidative ROS. Silence of SIRT3 gene also suppressed AKT-dependent ferroptosis, an iron-dependent and lipid peroxide-mediated cell death. Blockade of AKT activity in sh-SIRT3 cells induced ACSL4 expression that drives ferroptosis, and inhibited epithelial-mesenchymal (EMT) markers and invasive activity. In contrast, overexpression of SIRT3 led to the opposite effects on mitochondrial metabolism and EMT. Finally, transplantation of sh-SIRT3 cells in nude mice resulted in rapid tumor growth and larger tumors that expressed lower E-cadherin and lipid peroxide 4-hydroxynonenal (4-HNE) than those observed in control tumors. Collectively, our studies indicate that SIRT3 functions to inhibit AKT-dependent mitochondrial metabolism and EMT, leading to ferroptosis and tumor suppression.
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http://dx.doi.org/10.1016/j.canlet.2021.04.007DOI Listing
July 2021

Evaluation of Cervical High-Grade Squamous Intraepithelial Lesions-Correlated Markers as Triage Strategy for Colposcopy After Co-Testing.

Onco Targets Ther 2021 19;14:2075-2084. Epub 2021 Mar 19.

Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.

Background: Colposcopy was referred in cases with severe abnormalities in co-testing. Although p16/Ki67 dual staining reduced the referral rate, its sensitivity and specificity need to be enhanced.

Methods: The expressions of p16, Ki-67, SMAD3, YAP1, RELA were evaluated in the colposcopy referral population. The inclusion criteria included 30-60 years and diagnosed with HPV16/18-positive, other HR-HPV-positive with ASCUS, LSIL, AGC (atypical glandular cell) in co-testing. Colposcopies, endocervical curettages of cervical biopsies were also collected. Cases were excluded if there were no biopsies, if the interval between a cervical screening test and biopsies was more than 6 months, or if insufficient tissue was available as a formalin-fixed paraffin-embedded block. The pathology was independently reviewed by two pathologists. Discrepant interpretations were adjudicated by a third pathologist.

Results: In total, 1194 of 1273 cases who were referred to colposcopy were evaluated in the present study. The sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 62.1% and 89.5%, respectively. p16+ combined with YAP1+ and/or RELA+ provided a sensitivity and specificity of 70.9% and 89.5%, respectively, while 72.8% and 86.4% were achieved by p16+ combined with YAP1+ and/or SMAD3+ and/or RELA+. In HPV16/18+ and LSIL subgroups, the sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 67.7% and 87.6%, respectively, for the former group and 58.6%, 88.8%, respectively, for the latter group. p16+, YAP1+/RELA+ showed a better performance for predicting CIN2+ with a better sensitivity and considerable specificity in the other HPV+ combined with ASCUS group than were achieved by p16+ combined with Ki-67+. RELA+ and the combination of p16 and RELA/YAP1 also provided the Max AUC area.

Conclusion: Our study shows that RELA and the combination of p16 and RELA/YAP1 achieved better sensitivity and specificity for detecting morphologically CIN2+ lesions.
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http://dx.doi.org/10.2147/OTT.S300269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989978PMC
March 2021

Oncological and Reproductive Outcomes of Cystectomy Compared with Unilateral Salpingo-Oophorectomy as Fertility-Sparing Surgery in Patients with Apparent Early Stage Pure Immature Ovarian Teratomas.

Ann Surg Oncol 2021 Mar 26. Epub 2021 Mar 26.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China.

Purpose: To compare the oncological and reproductive outcomes of patients with apparent early stage pure ovarian immature teratomas (IMTs) treated with unilateral salpingo-oophorectomy (USO) or cystectomy.

Patients And Methods: We retrospectively reviewed the medical records of patients with apparent early stage pure ovarian IMTs who received fertility-sparing surgery (FSS) between 1984 and 2019. FSS was defined as preservation of the uterus and at least one adnexa. Recurrence rates were compared between patients receiving USO and cystectomy. Reproductive outcomes and menstrual histories were assessed by telephone interview.

Results: A total of 124 patients were included, of whom 83 underwent USO and 41 underwent cystectomy. After a median follow-up of 70.6 months (range: 6.2-410.6 months), eight patients suffered recurrences (5 in the USO group and 3 in the cystectomy group). The median times to recurrence were 5.0 and 5.1 months in the USO and cystectomy groups, respectively (P = 0.764). All patients with recurrence were successfully salvaged by surgery, except for one death. Univariate analysis showed no difference in disease-free survival and overall survival between the groups (P = 0.781, 0.155). Of the 111 patients contacted by telephone, 97 resumed menstruation following the surgery. Of the 31 patients desiring pregnancy, 26 achieved 28 pregnancies. USO (83.3%), like cystectomy (85.7%), resulted in excellent pregnancy rates.

Conclusions: A USO is the standard treatment for women with early stage pure IMTs who want to preserve fertility. However, a cystectomy with adjuvant chemotherapy may be a suitable fertility-sparing therapy when a cystectomy is the only surgical option.
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http://dx.doi.org/10.1245/s10434-021-09719-zDOI Listing
March 2021

Alpha-fetoprotein (AFP)-producing epithelial ovarian carcinoma (EOC): a retrospective study of 27 cases.

Arch Gynecol Obstet 2021 Mar 9. Epub 2021 Mar 9.

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.

Objective: The aim of the study was to investigate the relative risk factors associated with the prognosis and effective treatments of alpha-fetoprotein (AFP)-producing epithelial ovarian carcinoma (EOC).

Method: We presented three cases of AFP-producing EOC and performed a brief review to summarize the clinicopathological features and prognostic factors of 24 cases that have been previously reported. We evaluated the correlations among prognostic and clinical parameters, such as stage, pathology and chemotherapy regimens. In addition, a retrospective review of these 27 cases was conducted, and survival curves were estimated using the Kaplan-Meier method.

Results: The patients were aged between 23 and 77 years. The median overall survival was 10 months, and ten (37.04%) patients died within 18 months. We compared the overall mean survival times of all patients in different stages, and the results suggest that the postoperative pathological staging is hardly correlated with prognosis (P = 0.76). There was a correlation between pathology and prognosis (P = 0.0018). The mean survival time was longer for patients who had undergone chemotherapy than for those without chemotherapy (14.88 vs 0.65 months) (P < 0.0001). Moreover, although patients had a good response to the regimens for PEB and TC (P = 0.004), there was no significant difference between PEB and TC (P = 0.386).

Conclusions: AFP-producing EOC is uncommon and regarded as an extremely malignant type of tumor. Patients with chemotherapy may have a longer survival time; additionally, PEB and TC may be an optimal selection for this kind of tumor. Further large-scale studies are needed to confirm our findings.
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http://dx.doi.org/10.1007/s00404-021-06017-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942666PMC
March 2021

Identification of a Six-Gene Signature for Predicting the Overall Survival of Cervical Cancer Patients.

Onco Targets Ther 2021 5;14:809-822. Epub 2021 Feb 5.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

Background: Although the incidence of cervical cancer has decreased in recent decades with the development of human papillomavirus vaccines and cancer screening, cervical cancer remains one of the leading causes of cancer-related death worldwide. Identifying potential biomarkers for cervical cancer treatment and prognosis prediction is necessary.

Methods: Samples with mRNA sequencing, copy number variant, single nucleotide polymorphism and clinical follow-up data were downloaded from The Cancer Genome Atlas database and randomly divided into a training dataset (N=146) and a test dataset (N=147). We selected and identified a prognostic gene set and mutated gene set and then integrated the two gene sets with the random survival forest algorithm and constructed a prognostic signature. External validation and immunohistochemical staining were also performed.

Results: We obtained 1416 differentially expressed prognosis-related genes, 624 genes with copy number amplification, 1038 genes with copy number deletion, and 163 significantly mutated genes. A total of 75 candidate genes were obtained after overlapping the differentially expressed genes and the genes with genomic variations. Subsequently, we obtained six characteristic genes through the random survival forest algorithm. The results showed that high expression of , and and low expression of and were associated with a poor prognosis in cervical cancer patients. We constructed a six-gene signature that can separate cervical cancer patients according to their different overall survival rates, and it showed robust performance for predicting survival (training set: ˂ 0.001, AUC = 0.82; testing set: ˂ 0.01, AUC = 0.59).

Conclusion: Our study identified a novel six-gene signature and nomogram for predicting the overall survival of cervical cancer patients, which may be beneficial for clinical decision-making for individualized treatment.
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http://dx.doi.org/10.2147/OTT.S276553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873033PMC
February 2021

Could Adjuvant Chemotherapy Improve Prognosis for Cervical Cancer Patients with Elevated Pretreatment Serum Squamous-Cell Carcinoma Antigen?

Risk Manag Healthc Policy 2021 11;14:109-116. Epub 2021 Jan 11.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Objective: The aim of this study was to explore whether adjuvant chemotherapy could improve prognosis for cervical cancer patients with elevated pretreatment serum squamous-cell carcinoma antigen (SCC-Ag).

Methods: Propensity-score matching and inverse probability of treatment weighting (IPTW) were used to ensure balanced groups for patients with (arm A) and without adjuvant chemotherapy (arm B). All patients were treated between January 2012 and December 2014 at a single center. Study outcomes were disease-free survival (DFS) and overall survival (OS).

Results: In total, 81 patients were included in this study. By propensity-score matching, 35 patients were included in each group (arm A and arm B). Median follow-up was 60 months in arm A and 66 months in arm B. Overall, 85.7% of patients in arm A and 71.4% of those in arm B received adjuvant radiotherapy. DFS and OS curves were similar between arms A and B (=0.971 and 0.633, respectively). With IPTW, arm A was not associated with prognosis in terms of DFS (HR 0.946, 95% CI 0.237-3.784; =0.938) or OS (HR 1.020, 95%CI 0.357-2.913; =0.970).

Conclusion: For patients with elevated pretreatment SCC-Ag, adjuvant chemotherapy was not found to improve prognosis. Also, a considerable proportion of these patients had postoperative indications for adjuvant radiotherapy. For these cervical cancer patients with elevated pretreatment SCC-Ag, the choice of radical hysterectomy and adjuvant chemotherapy should be prudent.
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http://dx.doi.org/10.2147/RMHP.S273848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810669PMC
January 2021

Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer.

J Ovarian Res 2021 Jan 11;14(1):12. Epub 2021 Jan 11.

Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Zhejiang, China.

Objective: To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy.

Methods: This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints.

Results: Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2-6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4-46.4%), and the DCR was 65.2% (95% CI, 56.4-74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires.

Conclusions: For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.
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http://dx.doi.org/10.1186/s13048-020-00736-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798203PMC
January 2021

Identification of Somatic Mutations in Papanicolaou Smear DNA and Plasma Circulating Cell-Free DNA for Detection of Endometrial and Epithelial Ovarian Cancers: A Pilot Study.

Front Oncol 2020 14;10:582546. Epub 2020 Dec 14.

Berry Oncology Corporation, Beijing, China.

Objectives: The aim of this study was to identify tumor-derived DNA from Papanicolaou (Pap) smear and plasma specimens collected from patients with endometrial cancer or atypical hyperplasia (EC/AH) or epithelial ovarian cancer (OC).

Methods: Tumor tissues, peripheral blood, and Pap smear samples were collected from patients with EC/AH and patients with epithelial OC. Somatic mutations of tumor specimens in EC/AH and OC were examined by whole-exome sequencing using a 127-driver gene panel from The Cancer Genome Atlas (TCGA). A nine-gene EC/AH panel and an eight-gene OC panel were established based on the identified significantly mutated genes in the EC/AH and OC tumor specimens. Circulating single-molecule amplification and resequencing technology (cSMART) was applied to evaluate somatic mutations in Pap smear DNA and plasma circulating cell-free DNA (ccfDNA) using the EC/AH and OC gene panels.

Results: In EC/AH group, there existed 22 tumors and 14 of the 22 tumors contributed hot spot mutations for the EC/AH nine-gene panel. In the Pap smear subgroup, all 21 Pap smears tested positive. Nine out of 11 (81.8%) identified the same gene mutations with their matched tumors and the remaining 10 Pap smears all tested positive. In the plasma subgroup, 10 out of 26 (38.5%) plasmas tested positive. One out of 13 (7.7%) identified the same gene mutation with its matched tumor and 5 out of the remaining 13 plasmas (38.5%) tested positive. In OC group, there existed 17 tumors and 16 of the 17 tumors contributed hot spot mutations for the OC eight-gene panel. In the Pap smear subgroup, all 11 Pap smears tested positive. Five out of 10 (50.0%) identified the same gene mutations with their matched tumors and the remaining one Pap smear also tested positive. In the plasma subgroup, all 22 plasmas tested positive. Ten out of 14 (71.4%) identified the same gene mutation with their matched tumors and the remaining 4 plasmas all tested positive.

Conclusions: Tumor-derived DNA can be detected in Pap smears and plasmas from patients with EC/AH or epithelial OC. Using a small gene-panel, early detection of EC/AH and OC might be promising. However, the value of plasma ccfDNA for EC/AH requires further investigation.
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http://dx.doi.org/10.3389/fonc.2020.582546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768029PMC
December 2020

CYP27B1 Downregulation: A New Molecular Mechanism Regulating EZH2 in Ovarian Cancer Tumorigenicity.

Front Cell Dev Biol 2020 14;8:561804. Epub 2020 Oct 14.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Ovarian cancer has the highest mortality rate among gynecologic cancers, and most patients are diagnosed in advanced stages. Enhancer of zeste homolog 2 (EZH2) is a major tumor marker and an effective therapeutic target for ovarian cancer, but the underlying molecular mechanism remains unclear. The present study investigated the biological effects of EZH2 knockout in SKOV3 cells and and explored the molecular mechanism by integrated analysis of messenger RNA sequencing (mRNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) data.

Methods: The CRISPR/Cas9 system was used to establish EZH2 knockout SKOV3 cells. Protein expression was evaluated by Western blotting. The effect of EZH2 on ovarian cancer was evaluated with MTT, wound healing, Transwell, and apoptosis assays and with a xenograft model. mRNA-seq and ChIP-seq were performed to explore the molecular mechanism underlying the biological function of EZH2. Immunohistochemical staining (IHC) of tissue arrays was used to analyze the correlations among EZH2 and CYP27B1 expressions and prognosis.

Results: We obtained three EZH2 knockout subclones. EZH2 knockout SKOV3 cells exhibited significantly suppressed proliferation, migration, and invasion and a significantly increased apoptosis rate. The subcutaneous tumor formation rate decreased from 100 to 0% in the EZH2 knockout group. Integrated analysis of the mRNA-seq and ChIP-seq data identified 1,455 significantly upregulated genes with matching downregulated trimethylation of histone H3 lysine 27 (H3K27me3) methylation binding sites in 1b11H cells compared to SKOV3 cells. The set of downregulated genes in EZH2 knockout cells was highly enriched in genes regulating the activation of steroid biosynthesis; the top-ranked hub gene was CYP27B1. The EZH2 and CYP27B1 expression levels showed a statistically significant inverse correlation, which was also associated with unfavorable prognosis. The experiment demonstrated that CYP27B1 can suppress the proliferation, migration, and invasion of ovarian cancer cells. Moreover, the levels of AKT and p-AKT were significantly increased, whereas STAT3 was downregulated, in 1b11H cells compared to SKOV3 cells. Moreover, STAT3 and AKT overexpression was observed in 1b11H siRNA for CYP27B1 (siCYP27B1) cells.

Conclusion: EZH2 plays an important role in promoting cell proliferation, migration, and invasion in ovarian cancer by regulating the core steroid biosynthesis gene H3K27me3 methylation. Moreover, CYP27B1, the steroid biosynthesis hub gene, might be a novel therapeutic target for ovarian cancer.
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http://dx.doi.org/10.3389/fcell.2020.561804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591459PMC
October 2020

Clinical Characteristics and Mutation Analyses of Ovarian Sertoli-Leydig Cell Tumors.

Oncologist 2020 09 11;25(9):e1396-e1405. Epub 2020 Aug 11.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Background: There are limited studies on Sertoli-Leydig cell tumors (SLCTs) and no data in the population of Chinese patients with SLCTs from the genetic level. In addition, previous studies on SLCTs have focused exclusively on mutations in the DICER1 gene and no data exists on the genetic landscape of SLCTs.

Methods: Patients with moderately or poorly differentiated SLCTs who underwent surgical resection between January 2012 and October 2018 in our institution were recruited. Whole exome sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue and peripheral blood or normal tissue samples.

Results: Seventeen patients were recruited with 19 tumor samples. The rate of tumor-associated germline mutations was 6 of 17 (35.3%), and that of DICER1 germline mutations was 4 of 17 (23.5%). Regarding clinical relapse, patients with germline tumor-associated mutations had significantly poorer prognosis than those without (p = .007), and those with germline DICER1 mutations were relatively more likely to exhibit clinical relapse, although not to a significant degree (p = .069). Regarding somatic mutations, firstly, the subclone evolution analysis demonstrated that the two tumors on the contralateral ovary were primary tumors, respectively. Secondly, somatic mutations were most commonly found in CDC27 (10/19, 52.6%), DICER1 (4/19, 21.1%), and MUC22 (4/19, 21.1%). And the analysis of cancer cell fractions showed that DICER1 mutations were correlated with tumorigenesis of SLCTs. The rates of germline and somatic DICER1 mutations were higher in patients who were younger than 18 years than those in older patients (p = .022 and p = .001, respectively).

Conclusion: Our study indicates that genetic testing may have important clinical significance for patients with SLCTs, particularly for younger patients.

Implications For Practice: Bilateral ovarian Sertoli-Leydig cell tumors were verified to be primary tumors from the genetic perspective. The rates of germline and somatic DICER1 mutations were 4 of 17 (23.5%) and 4 of 19 (21.1%), respectively. The rates of germline and somatic DICER1 mutations were higher in patients who were younger than 18 years than those in older patients (p = .022 and p = .001, respectively).
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http://dx.doi.org/10.1634/theoncologist.2020-0110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485360PMC
September 2020

Oncologic and Reproductive Outcomes of Uterine Smooth Muscle Tumor of Uncertain Malignant Potential: A Single Center Retrospective Study of 67 Cases.

Front Oncol 2020 14;10:647. Epub 2020 May 14.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The term "uterine smooth muscle tumor of uncertain malignant potential" (STUMP) indicates a rare tumor that cannot be classified as a benign leiomyoma or malignant leiomyosarcoma. In this study, we assessed the clinical characteristics, fertility, and oncologic outcomes of patients diagnosed as STUMP in 14 years. In addition, we analyzed the risk factors for recurrence in patients with STUMP. Medical records of STUMP patients at Peking Union Medical College Hospital (PUMCH) between January 2005 and June 2019 were reviewed and analyzed. Disease-free survival, age of diagnosis, tumor size, surgical procedure, pathology and immunohistochemistry, clinical characteristics, recurrence rate, and reproductive outcomes in the follow-up period were assessed. Univariate and multivariate analyses were performed to determine the prognostic factors. The median age was 42 years old (range: 21-63). Total hysterectomy with or without bilateral salpingo-oophorectomy was performed in 29/67 cases (43.3%), and myomectomy was performed in 38/67 cases (56.7%). Ten patients experienced recurrences, and all but two recurrences occurred within 5 years after the initial surgery. Only two of these recurrences were leiomyosarcoma. There were no deaths in the median follow-up period of 48.4 (range 2.6-170.2) months. There were no remarkable differences in location of tumor between the myomectomy and hysterectomy groups, but the patients in the myomectomy group were younger than those in the hysterectomy group. In univariate and multivariate analysis, mitosis on pathology was the only independent risk factor for recurrence. Expression of Ki-67, p53, and p16 was significantly higher in patients with recurrence. Seven of the 35 patients who attempted to conceive had successful pregnancies. The prognosis of STUMP was favorable and tumors with more than 10 mitoses per 10 high power field should be monitored closely. The surgical procedure was not an independent risk factor of recurrence, and myomectomy may be an acceptable option for patients wishing to preserve fertility.
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http://dx.doi.org/10.3389/fonc.2020.00647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240040PMC
May 2020

Clinicopathological features and maternal and foetal management of pregnancy-complicating Krukenberg tumours.

Mol Clin Oncol 2020 Jun 30;12(6):581-587. Epub 2020 Mar 30.

Department of Gynecology and Obstetrics, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Dongcheng, Beijing 100730, P.R. China.

Krukenberg tumours are not uncommon, but pregnancy-complicating Krukenberg tumours are rare. To identify management strategies of pregnancies with Krukenberg tumours, the medical records of patients treated at Peking Union Medical College Hospital over the past 20 years were collected and analysed. Four patients were enrolled. The primary tumour sites were the stomach and colorectal region. Three patients presented with obvious and severe gastrointestinal symptoms at 11-18 weeks of gestation, and their symptoms gradually developed into physiological signs associated with malignancy. Three patients underwent termination of pregnancy via induced delivery and gestational hysterectomy. One patient underwent caesarean section at 31 weeks of gestation. Two patients underwent palliative surgery due to extensive lesions. The other two patients with metastatic lesions confined to the ovaries and liver, underwent satisfactory cytoreductive surgery and anti-tumour treatments postoperatively. Pregnant women who exhibit new gastrointestinal symptoms or aggravation of previous gastrointestinal symptoms after the end of the first trimester should be carefully examined for digestive system diseases. If ovarian metastasis is highly suspected, the pregnancy should be terminated as early as possible.
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http://dx.doi.org/10.3892/mco.2020.2025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179388PMC
June 2020

Distinct gene expression profiles associated with clinical outcomes in patients with ovarian clear cell carcinoma and high-grade serous ovarian carcinoma.

J Ovarian Res 2020 Apr 15;13(1):38. Epub 2020 Apr 15.

Department of Gynaecologic Oncology, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng-qu, Beijing, People's Republic of China.

Background: Ovarian clear cell carcinoma (OCCC) is the second most common ovarian cancer after serous carcinoma in Southeast Asia. OCCC has a more unfavourable clinical outcome due to a poor response to platinum-based chemotherapy compared with serous carcinoma. The identification of biomarkers related to the prognosis of OCCC is critically important for an improved understanding of the biology that drives OCCC progression and leads to poor outcomes. To detect differences in gene expression profiles between OCCC and high-grade serous ovarian carcinoma (HGSOC), twelve patients with OCCC and twelve patients with HGSOC were recruited in whom the pathological diagnosis was confirmed on surgically resected specimens.

Results: Compared with HGSOC, OCCC has 609 differentially expression genes, and 199 are significantly different (P < 0.05). These genes are involved in the cell cycle, apoptosis, DNA damage repair, the PI3K pathway and so on. There were 164 differentially expressed genes in the PI3K pathway. There were 35 overexpressed genes in OCCC, while there were 12 overexpressed genes in HGSOC. Among these differentially expressed genes, we found that the MET gene and the CCNE1 gene were overexpressed in OCCC and associated with a worse prognosis.

Conclusions: In conclusion, there are many differentially expressed genes in OCCC and HGSOC, which indicates that the two kinds of tumours differ greatly in tumourigenesis and provides a theoretical basis for targeted therapy in the future. Further studies need to be performed to clarify the association of the differentially expressed genes with the unfavourable prognosis in OCCC.
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http://dx.doi.org/10.1186/s13048-020-00641-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161165PMC
April 2020

Outcomes and prognostic factors of patients with recurrent and persistent malignant ovarian germ cell tumors.

Arch Gynecol Obstet 2020 04 20;301(4):1021-1026. Epub 2020 Mar 20.

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Objective: Due to the rarity of recurrent and persistent malignant ovarian germ cell tumors (MOGCTs), there is no standardized protocol for salvage therapy. This study aimed to investigate the outcomes and prognostic factors of patients with recurrent and persistent MOGCTs.

Methods: Clinical data for 59 patients with recurrent and persistent MOGCTs admitted to Peking Union Medical College Hospital from January 1, 2000, to April 30, 2018, were retrospectively analyzed.

Results: Twenty-one cases (35.6%) were recurrent, and 38 (64.4%) were persistent. Patient age ranged from 1 to 39 years, and disease stage was as follows: 33 stage I, 4 stage II, 21 stage III, and 1 stage IV. There were 19 immature teratomas, 26 yolk sac tumors, 1 dysgerminoma, and 13 mixed germ cell tumors. Regarding the primary surgery, fertility was preserved in 49 patients and not preserved in 10 patients. Among the patients who underwent fertility-preserving primary surgery, 40 had fertility preserved in the second operation, and 9 did not. In the mean follow-up of 52.6 months (range 2-279 months) after recurrence, 19 patients (32.2%) experienced a second relapse, and 16 (27.1%) died. The 5-year survival and progression-free survival rates after relapse were 70.0% and 67.0%, respectively. The optimal salvage surgery and chemotherapy regimen after relapse were independent prognostic factors (P < 0.05).

Conclusions: The prognosis of recurrent and persistent MOGCTs was good after salvage therapy. The optimal salvage surgery and adjuvant standardized chemotherapy significantly impact patient prognosis. For young nulliparous patients, secondary fertility-sparing salvage therapy can be considered.
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http://dx.doi.org/10.1007/s00404-020-05452-2DOI Listing
April 2020

Role of staging surgery and adjuvant chemotherapy in adult patients with apparent stage I pure immature ovarian teratoma after fertility-sparing surgery.

Int J Gynecol Cancer 2020 05 15;30(5):664-669. Epub 2020 Mar 15.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Objective: The standard treatment for young patients with stage I malignant ovarian germ cell tumors, except stage I dysgerminoma and stage IA G1 immature teratoma, is unilateral salpingo-oophorectomy with complete staging surgery followed by platinum-based chemotherapy. However, the role of complete staging surgery and adjuvant chemotherapy remains controversial. The aim of this study was to investigate the role of complete staging surgery and adjuvant chemotherapy in patients with early-stage pure immature teratoma after fertility-sparing surgery.

Methods: Patients with stage I pure immature teratoma who underwent fertility-sparing surgery between January 1986 and June 2018 were reviewed retrospectively. Fertility-sparing surgery was defined as preservation of the uterus and at least one adnexa. The inclusion criteria were age >18 years, stage I disease (confined to one ovary), and diagnosis of pure immature teratoma. Patients with distant metastasis or mixed ovarian germ cell tumor were excluded. Complete staging surgery was defined as peritoneal cytology examination, peritoneal biopsy, omentectomy, or omental biopsy with or without lymph node dissection. Patients designated with stage I disease without complete staging surgery were categorized as stage X. Disease-free survival was defined as the interval from the date of surgery to the date of recurrence or censoring. Disease-free survival curves were calculated using the Kaplan-Meier method and compared using the log-rank test.

Results: A total of 75 patients were included in the analysis, with a median age of 26 years (range 18-40): 26 (34.7%) patients had received complete staging surgery; 51 (68%) patients received postoperative adjuvant chemotherapy while 24 (32%) underwent surgery alone; and 4 patients (5.3%) had recurrent disease during a median follow-up time of 80.2 months (range 13.7-261). The recurrence rates in the chemotherapy group and surveillance groups were 3.9% and 8.3%, respectively (p=0.46). All patients were successfully salvaged, except for one death. Tumor relapse occurred in patients with all grades of immature teratoma (G1: 1/35; G2: 2/25; G3: 1/15). Univariate analysis revealed that complete staging surgery, adjuvant chemotherapy, and tumor grade were not associated with 5 year disease-free survival (p=0.69, p=0.46, p=0.7, respectively). The 5 year disease-free survival rate was 94.6% and the overall survival rate was 98.7%.

Conclusion: Adult patients with stage I pure immature teratoma had 98.7% overall survival and recurrence rates were low after fertility-sparing surgery.
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http://dx.doi.org/10.1136/ijgc-2019-001116DOI Listing
May 2020

Importance of Standard Treatment in Prognosis of Patients with Ovarian Cancer and Associated Cerebral Infarction.

Clin Interv Aging 2020 5;15:151-157. Epub 2020 Feb 5.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Objective: Data on the treatment of patients with ovarian cancer (OC) and associated cerebral infarction (CI) are extremely limited. The objectives were to investigate the risk factors for prognosis in patients with OC and associated CI.

Methods: We retrospectively reviewed the electronic medical records of patients with OC from January 2013 to November 2018 in Peking Union Medical Hospital.

Results: In total, 2632 inpatients were diagnosed with malignant ovarian cancer in our institution, and 30 patients (1.1%) were diagnosed with OC-associated CI. The median age was 60 years (range, 37-83). The standard treatment, according to National Comprehensive Cancer Network (NCCN) guidelines, was administered to 19 patients. The median follow-up time was 19.5 months (range, 1-59 months). In total, 17 patients experienced tumor progression, and 16 of them died. In univariate analysis, overall survival was significantly associated with the D-dimer level (P=0.017), FIGO stage (P=0.014), complete cytoreduction (P<0.000) and standard treatment (P<0.000). In multivariate analysis, the standard treatment remained an independent protective factor for death (hazard ratio=0.061, 95% confidence interval=0.007-0.537, P=0.012).

Conclusion: Although the prognosis of patients with OC and associated CI was poor, those who underwent the standard treatment still benefited.
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http://dx.doi.org/10.2147/CIA.S229236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014957PMC
August 2020

Diagnosis and management of growing teratoma syndrome after ovarian immature teratoma: A single center experience.

Gynecol Oncol 2020 04 15;157(1):94-100. Epub 2020 Jan 15.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, People's Republic of China. Electronic address:

Objectives: To evaluate the diagnostic, surgical, and oncological outcomes of patients with growing teratoma syndrome (GTS).

Methods: Patients diagnosed with ovarian immature teratoma (IMT) between 1980 and 2018 at Peking Union Medical College Hospital (PUMCH) were evaluated for the development of GTS. Their clinical characteristics, surgical and pathological data, and oncological outcomes were collected.

Results: Between 1980 and 2018, 175 cases of IMT were referred to PUMCH. Thirty-five patients subsequently developed GTS with a crude rate of approximately 20%. The median interval between the initial diagnosis of IMT and the first occurrence of GTS was 18.5 months (range, 6-78 months). Residual disease (P < 0.001) and gliomatosis peritonei (GP) at initial surgery (P = 0.023) were independent risk factors for GTS development. Fertility-sparing surgery for GTS was performed in 27 patients and four patients achieved five singleton pregnancies. The median follow-up time was 73 months (range, 11-401 months). Eleven patients developed at least one recurrence. Residual disease after GTS surgery was associated with GTS recurrence (P = 0.001). By the end of follow-up, 27 patients were alive without disease and the other eight patients were alive with disease.

Conclusion: The presence of residual disease and GP at initial surgery are risk factors for GTS. Complete surgical resection is the cornerstone for treatment of GTS. The presence of residual disease after surgery for GTS is a risk factor for GTS recurrence. Fertility-sparing surgery should be performed because spontaneous pregnancy is possible. The overall prognosis of GTS is excellent.
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http://dx.doi.org/10.1016/j.ygyno.2019.12.042DOI Listing
April 2020

Completion hysterectomy after chemoradiotherapy for locally advanced adeno-type cervical carcinoma: updated survival outcomes and experience in post radiation surgery.

J Gynecol Oncol 2020 Mar 17;31(2):e16. Epub 2019 Sep 17.

Department of Radiation Oncology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China.

Objective: To compare patient survival outcomes between completion hysterectomy and conventional surveillance in locally advanced adenocarcinoma of the cervix after concurrent chemoradiotherapy (CCRT).

Methods: Patients with adenocarcinoma of the cervix after CCRT were identified in a tertiary academic center database from 2004 to 2018. Patients received completion hysterectomy or surveillance after CCRT. We compared the progression-free survival (PFS) and overall survival (OS) between the patients with or without adjuvant hysterectomy. Surgery features, operative complications, and pathologic characteristics were documented. Patient outcomes were also analyzed according to clinicopathologic factors.

Results: A total of 78 patients were assigned to completion surgery and 97 to surveillance after CCRT. The PFS was better in the surgery group compared to the CCRT only group, at 3 years the PFS rates were 68.1% and 45.2%, respectively (hazard ratio [HR]=0.46; 95% confidence interval [CI]=0.282-0.749; p=0.002). Adjuvant surgery was also associated with a higher rate of OS (HR=0.361; 95% CI=0.189-0.689; p=0.002), at 3 years, 87.9% and 67%, respectively. Tumor stage, size, lymph-vascular space invasion (LVSI), lymphadenopathy were associated with PFS but not with OS. Hysterectomy specimens revealed 64.1% (50/78) of the patients had pathologic residual tumor. Patients age less than 60, tumor size over 4 cm, stage IIB and persistent residual disease after CCRT were most likely to benefit from hysterectomy. Hysterectomy was associated with a lower rate of locoregional recurrence but did not reach statistical significance (5.13% vs. 13.5%, p=0.067).

Conclusion: Completion hysterectomy after CCRT was associated with better survival outcome compared with the current standard of care.
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http://dx.doi.org/10.3802/jgo.2020.31.e16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044008PMC
March 2020

Clinical and Expression Significance of AKT1 by Co-expression Network Analysis in Endometrial Cancer.

Front Oncol 2019 6;9:1147. Epub 2019 Nov 6.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Endometrial cancer is one of the most common uterine cancers worldwide. AKT is reported to regulate progesterone receptor B dependent transcription and angiogenesis in endometrial cancer. However, the potential mechanisms of AKT in the tumor progression of endometrial cancer remain unclear. We used GSE72708 with gene expression profiles of AKT regulation from the GEO database. We performed GSEA analysis to explore pathway enrichments. We found that most upregulated enriched pathways in siAKT group were associated with acid metabolism and immune network. Endometrial cancer and various signaling pathways were downregulated enriched. Moreover, different molecular mechanism of regulation between progestin (R5020) and AKT was identified, which were related to VEGF signaling pathway. The hub genes were evaluated by immunohistochemical staining of endometrial cancer tissues. We screened out a total of 623 differentially expressed genes among different groups. According to weighted gene co-expression network analysis (WGCNA) method, four distinct modules were identified. We found brown module showed a very high positive correlation with siAKT group and a very high negative correlation with R5020 group. A total of six hub genes including PBK, BIRC5, AURKA, GTSE1, KNSTRN, and PSMB10 were finally identified associated with AKT1. In addition, the data also shows that the higher expression of AKT1, GTSE1, BIRC5, AURKA, and KNSTRN is significantly associate with poor prognosis of endometrial cancer. Our study identified six hub genes related to the prognosis of endometrial cancer, which may provide new insights into the underlying biological mechanisms driving the tumorigenesis of endometrial cancer, especially in AKT1 regulation.
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http://dx.doi.org/10.3389/fonc.2019.01147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852383PMC
November 2019

Laparoscopic vs. Open Abdominal Radical Hysterectomy for Cervical Cancer: A Single-Institution, Propensity Score Matching Study in China.

Front Oncol 2019 30;9:1107. Epub 2019 Oct 30.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

To compare the surgical and oncologic outcomes between open abdomen radical hysterectomy (ARH) and laparoscopic radical hysterectomy (LRH) for cervical cancer. Retrospective observational study with propensity score matching was used to ensure balanced groups for ARH and LRH. One-hundred-and-ninety-eight women with cervical cancer, 99 treated using ARH and 99 using LRH, between January 2012 and December 2014. Outcomes included disease-free survival (DFS), overall survival (OS), intra-operative factors, post-operator recovery, urinary retention, and adverse events. Moreover, the inverse probability of the treatment weighting (IPTW) method was also used. Compared with ARH, LRH was associated with a lower volume of blood loss ( < 0.001) and transfusion rate ( < 0.001), with a broader resection of the parametrium ( < 0.001). Post-operatively, the time to first flatus was shorter for LRH than ARH ( < 0.001) but the rate of urinary retention was higher for LRH (22.2%) than ARH (8.1%; = 0.009). DFS and OS were similar between groups. By IPTW, laparoscopy was also not associated with poorer survival in terms of DFS (HR 1.52, CI 0.799-2.891, = 0.202) or OS (HR 0.942, HR 0.425-2.09, = 0.883). Compared with ARH, LRH provided better intra-operative and post-operative outcomes, with no significant difference in oncologic outcomes and survival. Urinary retention remains a clinical issue to improve with LRH. The technology of LRH has been improved in China to address the inconsistent results of oncologic outcomes in previous studies. Whether these improvements could be effective needs to be investigated in the future.
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http://dx.doi.org/10.3389/fonc.2019.01107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833183PMC
October 2019

Identification of a Prognostic Signature Associated With DNA Repair Genes in Ovarian Cancer.

Front Genet 2019 12;10:839. Epub 2019 Sep 12.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Ovarian cancer is a highly malignant cancer with a poor prognosis. At present, there is no accurate strategy for predicting the prognosis of ovarian cancer. A prognosis prediction signature associated with DNA repair genes in ovarian cancer was explored in this study. Gene expression profiles of ovarian cancer were downloaded from the GEO, UCSC, and TCGA databases. Cluster analysis, univariate analysis, and stepwise regression were used to identify DNA repair genes as potential targets and a prognostic signature for ovarian cancer survival prediction. The top genes were evaluated by immunohistochemical staining of ovarian cancer tissues, and external data were used to assess the signature. A total of 28 DNA repair genes were identified as being significantly associated with overall survival (OS) among patients with ovarian cancer. The results showed that high expression of XPC and RECQL and low expression of DMC1 were associated with poor prognosis in ovarian cancer patients. The prognostic signature combining 14 DNA repair genes was able to separate ovarian cancer samples associated with different OS times and showed robust performance for predicting survival (Training set: p < 0.0001, AUC = 0.759; Testing set: p < 0.0001, AUC = 0.76). Our study identified 28 DNA repair genes related to the prognosis of ovarian cancer. Using some of these potential biomarkers, we constructed a prognostic signature to effectively stratify ovarian cancer patients with different OS rates, which may also serve as a potential therapeutic target in ovarian cancer.
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http://dx.doi.org/10.3389/fgene.2019.00839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751318PMC
September 2019

Corrigendum: Uterine Adenosarcoma: A Retrospective 12-Year Single-Center Study.

Front Oncol 2019;9:657. Epub 2019 Jul 24.

Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

[This corrects the article DOI: 10.3389/fonc.2019.00237.].
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http://dx.doi.org/10.3389/fonc.2019.00657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668359PMC
July 2019

Identification of prognosis markers for endometrial cancer by integrated analysis of DNA methylation and RNA-Seq data.

Sci Rep 2019 07 9;9(1):9924. Epub 2019 Jul 9.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Endometrial cancer is highly malignant and has a poor prognosis in the advanced stage, thus, prediction of its prognosis is important. DNA methylation has rapidly gained clinical attention as a biomarker for diagnostic, prognostic and predictive purposes in various cancers. In present study, differentially methylated positions and differentially expressed genes were identified according to DNA methylation and RNA-Seq data. Functional analyses and interaction network were performed to identify hub genes, and overall survival analysis of hub genes were validated. The top genes were evaluated by immunohistochemical staining of endometrial cancer tissues. The gene function was evaluated by cell growth curve after knockdown CDC20 and CCNA2 of endometrial cancer cell line. A total of 329 hypomethylated highly expressed genes and 359 hypermethylated lowly expressed genes were identified, and four hub genes were obtained according to the interaction network. Patients with low expression of CDC20 and CCNA2 showed better overall survival. The results also were demonstrated by the immunohistochemical staining. Cell growth curve also demonstrated that knockdown CDC20 and CCNA2 can suppress the cell proliferation. We have identified two aberrantly methylated genes, CDC20 and CCNA2 as novel biomarkers for precision diagnosis in EC.
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http://dx.doi.org/10.1038/s41598-019-46195-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617448PMC
July 2019

Uterine Adenosarcoma: A Retrospective 12-Year Single-Center Study.

Front Oncol 2019 14;9:237. Epub 2019 May 14.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Lymphovascular space invasion is an independent risk factor for disease progression and presence of tumor stalk an independent protective factor. Fertility sparing surgery may be acceptable in cases whose tumors present with stalks and without high risk factors. The aim of the present study was to investigate the potential prognostic factors of uterine adenosarcoma. A total of 49 cases of uterine adenosarcoma were retrospectively reviewed at our institution between April 2006 and October 2018. Median follow-up time was 34 months (range: 1-148). Median age was 47.50 years (19-75). Nineteen (38.9%) patients were uterine cervical adenosarcoma and 30 (61.22%) patients were uterine corpus adenosarcoma. Twenty-nine (59.2%) patients were polypoid with a stalk to the uterine cervix or corpus. Twenty-six (38.8%) patients were stage IA. Fifteen (30.6%) patients showed sarcomatous overgrowth. Six (12.2%) patients displayed lymphovascular space invasion (LVSI). Four (8.16%) patients had heterologous elements. In univariate analysis, Disease-free-survival (DFS) was associated with tumor location, presence of tumor stalk, heterologous elements, LVSI. In multivariate analysis, presence of tumor stalk remained an independently protective factor for recurrence (HR = 0.088, = 0.005), and LVSI a risk factor for recurrence (HR = 11.953, = 0.002). Fertility-sparing surgery (FSS) was performed in seven stage IA patients. When patients of stage IA analyzed separately, FSS was not significant with the DFS or OS. Presence of tumor stalk remained an independently protective factor for recurrence. Along with adequate counseling, FSS may be acceptable in cases whose tumors present with stalks and without high risk factors.
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http://dx.doi.org/10.3389/fonc.2019.00237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527837PMC
May 2019

Uterine and Cervical Adenosarcoma: A Retrospective Study of Overall Oncologic Outcomes and Fertility Preservation in Early-Stage Disease.

Oncologist 2019 09 24;24(9):e870-e879. Epub 2019 May 24.

Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Background: The management of adenosarcoma is based on the limited available data. This study aimed to explore the characteristics and oncologic outcomes of patients with uterine and cervical adenosarcoma.

Materials And Methods: A total of 21 and 32 cases of cervical and uterine adenosarcoma, respectively, were retrospectively reviewed in Peking Union Medical College Hospital between April 2006 and March 2019.

Results: The median follow-up time was 37.5 months (range, 1-153 months). The disease progression rate (DPR) was significantly higher in patients with uterine adenosarcoma compared with those with cervical adenosarcoma (28.1% vs. 4.8%). The curve of progression-free survival significantly differed. For those with cervical adenosarcoma, the presence of a tumor stalk was a protective factor, whereas heterologous elements (HE) presented a risk factor for disease progression. For those with uterine adenosarcoma, the presence of a tumor stalk was an independent protective factor, whereas lymphovascular space invasion (LVSI) was an independent risk factor for disease progression. Moreover, HE was an independent risk factor for mortality. Fertility-sparing surgery (FSS) was performed in four and five patients with cervical and uterine adenosarcoma, respectively. Regarding FSS, combined with cases in previous studies, the DPR of patients with uterine adenosarcoma was relatively higher compared with those with cervical adenosarcoma.

Conclusion: We found that cervical adenosarcoma had a better prognosis than uterine adenosarcoma. The presence of a tumor stalk was a protective factor, whereas HE and LVSI were risk factors for prognosis. For those with uterine adenosarcoma, if FSS was administered, robust evaluation would be necessary. The small sample size limits the ability to make any strong conclusions about FSS.

Implications For Practice: Uterine cervical adenosarcoma had a better prognosis than uterine adenosarcoma. For patients with cervical adenosarcoma, the presence of a tumor stalk was a protective factor and the presence of heterologous elements (HE) was a risk factor for disease progression. For those with uterine adenosarcoma, the presence of a tumor stalk was a protective factor and lymphovascular space invasion was a risk factor for disease progression. Moreover, HE was a risk factor for mortality. Regarding fertility-sparing surgery (FSS), the disease progression rate was higher in patients with uterine adenosarcoma compared with those with cervical adenosarcoma. For patients with uterine adenosarcoma, if FSS was administered, hysteroscopy and robust imaging evaluation would be necessary.
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http://dx.doi.org/10.1634/theoncologist.2018-0791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738297PMC
September 2019

Progress in immunocytochemical staining for cervical cancer screening.

Cancer Manag Res 2019 22;11:1817-1827. Epub 2019 Feb 22.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,

Cervical cancer is one of the most common gynecological malignancies. In recent years, the implementation of cervical cancer screening has resulted in the effective control of cervical cancer incidence. However, many deficiencies still exist in the current screening techniques and strategies. With advancements in cervical cancer screening research, immunochemical staining to determine cervical cytology has shown a broader application prospect in the early screening for cervical cancer, especially for triage in cervical cancer screening.
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http://dx.doi.org/10.2147/CMAR.S195349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391129PMC
February 2019
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