Publications by authors named "Jiaming Che"

10 Publications

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Development and validation of an autophagy-related prognostic signature in esophageal cancer.

Ann Transl Med 2021 Feb;9(4):317

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Autophagy has a dual function in cancer, and its role in carcinogenesis of the esophagus remains poorly understood. In the present study, we explored the prognostic value of autophagy in esophageal cancer (ESCA), one of the leading causes of cancer-related deaths worldwide.

Methods: Using ESCA RNA-sequencing (RNA-Seq) data from 158 primary patients with ESCA, including esophageal adenocarcinoma and esophageal squamous cell carcinoma, were downloaded from The Cancer Genome Atlas (TCGA) for this study. We obtained differentially expressed autophagy-related genes (ARGs) by the "limma" package of R. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses unveiled several fundamental signaling pathways associated with the differentially expressed ARGs in ESCA. Univariate Cox regression analyses were used to estimate associations between ARGs and overall survival (OS) in the TCGA ESCA cohort. A Cox proportional hazards model (iteration =1,000) with a lasso penalty was used to create the optimal multiple-gene prognostic signature utilizing an R package called "glmnet".

Results: A prognostic signature was constructed with four ARGs (, , and ) in the training set, which significantly divided ESCA patients into high- and low-risk groups in terms of OS [hazard ratio (HR) =1.508, 95% confidence interval (CI): 1.201-1.894, P<0.001]. In the testing set, the risk score remained an independent prognostic factor in the multivariate analyses (HR =1.572, 95% CI: 1.096-2.257, P=0.014). The area under the curve (AUC) of the receiver operating characteristic (ROC) predicting 1-year survival showed a better predictive power for the prediction model. The AUC in training and testing cohorts were 0.746 and 0.691, respectively. Therefore, the prognostic signature of the four ARGs was successfully validated in the independent cohort.

Conclusions: The prognostic signature may be an independent predictor of survival for ESCA patients. The prognostic nomogram may improve the prediction of individualized outcome. This study also highlights the importance of autophagy in the outcomes of patients with ESCA.
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February 2021

The Prognostic Value of Tumor Mutation Burden and Immune Cell Infiltration in Thymic Epithelial Tumors.

Ann Clin Lab Sci 2021 Jan;51(1):44-54

Department of Thoracic Surgery, Ruijin Hospital; Shanghai Jiao Tong University School of Medicine, Shanghai, China

Objective: The question of whether the tumor mutation burden (TMB) is associated with either improved survival outcomes or improvement of immunotherapies remains controversial in various malignancies. The aim of this study is to investigate the genomic landscape of the relationship between TMB and immune cell infiltration in thymic epithelial tumors (TETs).

Methods: We downloaded somatic mutation data, transcriptome sequencing data, and clinical information of TETs from the Cancer Genome Atlas (TCGA) database. We assessed the abundance of 22 immune fractions between low-TMB (TMB-L) and high-TMB (TMB-H) groups using the "CIBERSORT" package.

Results: Missense mutation had the highest frequency of mutation among the nine variant classifications in TETs. Higher TMB levels were associated with poor survival outcomes (<0.05), and higher Masaoka stages (<0.05). More importantly, TMB levels were much higher in the thymic cancer than in thymoma (<0.01). The infiltration levers of naive CD4(+) T cells and regulatory T cells were significantly higher in the TMB-L group than in the TMB-H group, and this was further associated with better overall survival (OS) in patients with TETs.

Conclusion: The present study indicates that the prognosis of TMB-H patients with TETs is significantly poorer than is that of TMB-L patients, which might result from the different levels of infiltration of naive CD4(+) T cells and regulatory T cells.
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January 2021

Next-generation sequencing in thymic epithelial tumors uncovered novel genomic aberration sites and strong correlation between TMB and MSH6 single nucleotide variations.

Cancer Lett 2020 04 19;476:75-86. Epub 2020 Feb 19.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China. Electronic address:

Thymic epithelial tumors (TET) including thymomas and thymic carcinomas are rare, but they are common primary tumors in the anterior mediastinum. The etiology and tumorigenesis of TET remain unclear. To better understand the novel aberrations of this rare tumor and provide more significant mutation sites for targeted therapy, we performed next-generation sequencing detection on 55 patients with TET. Our results showed that most genes in 12 core pathways harbored aberrations of indeterminate potential. In 4 genes (ARID1A, KMT2C, TGFBR2 and MAP3K1), the indel frequency was above 90%. Dozens of genes, including TGFBR2, KMT2C, PRKDC, ATR, CHD2, SDHA, KDM5A, CHEK1, MSH6 and POLE, possessed frameshift indel with different frequencies in different hotspot sites, which could be the new targets of therapy for TET. For the first time, we revealed a strong correlation between the tumor mutational burden and single nucleotide variations, but not frameshift, on DNA mismatch repair gene MSH6 in TET.
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April 2020

Endoscope-assisted mediastinal drainage therapy for anastomosis leakage after esophagectomy: a retrospective cohort study.

Ann Transl Med 2019 Dec;7(23):747

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Background: Anastomosis leakage after esophagectomy is a major threat which leads to many subsequent complications even mortality. But current diagnosis and treatment methods are inefficient. This retrospective study aims to evaluate the utilization of endoscope-assisted mediastinal drainage therapy in treatment for anastomosis leakage after esophagectomy.

Methods: Between January 2014 and June 2018, 51 patients were confirmed anastomosis leakage using gastroscopy. Of them, 23 patients were treated with endoscope-assisted mediastinal drainage therapy (drainage group); and the other 28 patients received endoscope-assisted biomedical fibrin glue occlusion (occlusion group). Short-term clinical outcomes were examined. Factors related to length of postoperative hospitalization (LPH) was analyzed.

Results: Endoscope provided highly accurate information on the condition of anastomosis leakage. And there was no evidence that early endoscopy could cause damage to the anastomosis or gastric conduit. One patient from drainage group and two from occlusion group discharged against medical advice. Other 48 patients were completely cured without reoperation or mortality. The median LPH was 32 days in drainage group (range from 17 to 80 days) and 81 days in occlusion group (range from 32 to 190 days), respectively (P<0.05). Linear regression indicated statistically significant correlation between LPH and length from diagnosis to drainage or occlusion (R=0.688, P<0.001).

Conclusions: Endoscope-assisted mediastinal drainage therapy is a satisfactory treatment for anastomosis leakage. Early diagnosis and treatment may facilitate the recovery of anastomosis leakage and reduce LPH.
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December 2019

Early Outcomes of Robot-Assisted Versus Thoracoscopic-Assisted Ivor Lewis Esophagectomy for Esophageal Cancer: A Propensity Score-Matched Study.

Ann Surg Oncol 2019 May 6;26(5):1284-1291. Epub 2019 Mar 6.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Both robot-assisted Ivor Lewis esophagectomy (RAILE) and conventional thoracoscopic-assisted Ivor Lewis esophagectomy (TAILE) are minimally invasive surgical techniques for the treatment of middle and distal esophageal cancer. However, no research studies comparing early outcomes between RAILE and TAILE have been reported.

Methods: A retrospective analysis was made of 184 patients, 76 in the RAILE group and 108 in the TAILE group, who underwent minimally invasive Ivor Lewis esophagectomy between December 2014 and June 2018. Propensity score-matched analysis was performed between the two groups based on demographics, comorbidities, American Society of Anesthesiologists score, tumor location, tumor size, and pathological stage. Perioperative outcomes were compared.

Results: Two conversions to thoracotomy occurred in the RAILE group. There was no 30-day in either group. Sixty-six matched pairs were identified for each group. Within the propensity score-matched cohorts, the operative time in the RAILE group was significantly longer than that in the TAILE group (302.0 ± 62.9 vs. 274.7 ± 38.0 min, P = 0.004). There was no significant difference in the blood loss [200.0 ml (interquartile range [IQR], 100.0-262.5 ml) vs. 200.0 ml (150.0-245.0 ml), P = 0.100], rates of overall complications (28.8 vs. 24.2%, P = 0.554), length of stay [9.0 days (IQR 8.0-12.3 days) vs. 9.0 days (IQR 8.0-11.3 days), P = 0.517], the number of total dissected lymph nodes (19.2 ± 9.2 vs. 19.3 ± 9.5, P = 0.955), and detailed categories of lymph nodes.

Conclusions: RAILE demonstrated comparable early outcomes compared with TAILE and should be considered as an alternative minimally invasive option for treating esophageal cancer.
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May 2019

Detection of Epithelial-Mesenchymal Transition Status of Circulating Tumor Cells in Patients with Esophageal Squamous Carcinoma.

Biomed Res Int 2018 26;2018:7610154. Epub 2018 Jun 26.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.

Purpose: To investigate the correlation between the status of epithelial-mesenchymal transition (EMT) of circulating tumor cells (CTCs) and esophageal squamous cell carcinoma (ESCC).

Methods: The demographic data and blood samples of 21 patients with ESCC were collected retrospectively. CTCs were enriched by using optimized CanPatrolTM CTC enrichment technique. CTCs were identified and characterized according to the EMT markers (e-CTCs: epithelial CTCs; mix-CTCs: epithelial-mesenchymal-mixed CTCs; m-CTCs: mesenchymal CTCs). The correlation between CTCs and demographic data was analyzed.

Results: Total 129 CTCs were detected in all the patients: 11(8.5%) CTCs of them were e-CTCs, 76(58.9%) were mix-CTCs, and 42(32.6%) were m-CTCs. The average number of CTCs from each patient was 6.1 ± 7.1 which included 0.5 ± 0.9 of e-CTCs, 3.6 ± 5.2 of mix-CTCs, and 2.0 ± 2.7 of m-CTCs; the difference between the three groups was significant ( = 0.017): the number of total CTCs was correlated with the number of mix-CTCs (2 = 0.883, < 0.01) and m-CTCs (2 = 0.639, < 0.01) but not e-CTCs (2 = 0.012, = 0.641) and the number of CTCs was correlated with the N stage and TNM stage in this study (2 = 0.698 and 2 = 0.359).

Conclusions: Mix-CTCs and m-CTCs might play an important role in progression of ESCC; the number of CTCs in ESCC might have the potential to be a predictor of prognosis.
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January 2019

Effects of Chinese Medicine as Adjunct Medication for Adjuvant Chemotherapy Treatments of Non-Small Cell Lung Cancer Patients.

Sci Rep 2017 04 24;7:46524. Epub 2017 Apr 24.

Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

The aim was to evaluate the effects of traditional Chinese medicine (TCM) as a combination medication with adjuvant chemotherapy on postoperative early stage non-small cell lung cancer (NSCLC) patients. The 314 patients with completely resected stage IB, II or IIIA cancers were assigned into vinorelbine plus cisplatin/carboplatin (NP/NC) (control, n = 158) and NP/NC with additional TCM (intervention, n = 156) groups. The primary endpoint was QOL scores; secondary endpoints were the toxicity and safety of the regimens. The NP/NC regimen caused mild (grade 1 or 2) non-hematologic toxic effects in the patients comprising vomiting (43.6%), fatigue (36.9%), pain (23%), dry mouth (27.6%) and diarrhea (7.9%). The incidence of adverse events was significantly lower in the intervention group than in the control group (0.57% vs 4.02%, P = 0.037). Transient severe (grade 3 or 4) hematological toxic effects occurred less often (hemoglobin reduction (11.9 vs 22.5 percent) and total bilirubin increased (to 42.1 vs 46.2%) in the intervention compared to the control group during the 2nd chemotherapy cycle. When combined with adjuvant chemotherapy, TCM led to partial relief of symptoms in addition to a reduction of side-effects and adverse events caused by the NP/NC regimens.
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April 2017

Surgical treatment of ectopic adrenocorticotropic hormone syndrome with intra-thoracic tumor.

J Thorac Dis 2016 May;8(5):888-93

Department of Thoracic Surgery, Shanghai Jiaotong University Medical School affiliated Ruijin Hospital, Shanghai 200025, China.

Background: The study was to review the clinical manifestations and laboratory examinations of ectopic adrenocorticotropic hormone (ACTH) syndrome, and to analyze the efficacy of surgical treatment.

Methods: The clinical data, surgical therapy, and outcome of 23 cases of ectopic ACTH syndrome accompanied by intra-thoracic tumors were reviewed. The tumors were removed from all the patients according to the principles of radical resection.

Results: The tumors were confirmed as associated with ectopic ACTH secretion in 19 cases. Hyperglycemia and hypokalemia were recovered, while plasma cortisol, plasma ACTH and 24-hour urinary free cortisol (UFC) levels were significantly reduced after surgery in these 19 cases. Recurrences of the disease were found in six cases during following-up, and five of them died.

Conclusions: The thoracic cavity should be a focus in routine examinations of patients with symptoms of Cushing's syndrome (CS), because ectopic ACTH-producing tumors are commonly found in bronchus/lung and mediastinum. Despite the incidence of the pulmonary nodule secondary to opportunistic infection in some cases, surgery is still the first choice if the tumor is localized. The surgical procedure should be performed according to the principles in resection of lung cancer and mediastinal tumor. The surgical efficacy is significant for short-term periods; however, the recurrence of the disease in long-term periods is in great part related to distal metastasis or relapse of the tumor.
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May 2016

Overexpression of ACE2 produces antitumor effects via inhibition of angiogenesis and tumor cell invasion in vivo and in vitro.

Oncol Rep 2011 Nov 18;26(5):1157-64. Epub 2011 Jul 18.

Department of Respiration, Shanghai Institute of Endocrinology, State Key Laboratory of Medical Genomics, Shanghai 200025, PR China.

Angiotensin II (AngII) is a multifunctional bioactive peptide in the renin-angiotensin system (RAS). Angiotensin-converting enzyme 2 (ACE2) is a newly identified component of RAS. The role of AngII and ACE2 in the metastasis of non-small cell lung cancer (NSCLC) and the effects on matrix metalloproteinases (MMPs) are still unknown. In the present study, the anti-invasive effect and mechanism of ACE2 were investigated in vitro and in vivo. Results of a transwell assay showed that the overexpression of ACE2 reduces the invasive ability of A549 cells in vitro. According to the results of qRT-PCR and western blot analysis, the inhibitory role of ACE2 was mediated through the down-regulation of MMP-2 and MMP-9. Additionally, we confirmed that the overexpression of ACE2 inhibited cell growth and VEGFa production while simultaneously suppressing ACE and angiotensin II type 1 receptor (AT1R) expression in human lung cancer xenografts. These results suggest that the overexpression of ACE2 may potentially suppress the invasion and angiogenesis of NSCLC.
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November 2011

The angiotensin-converting enzyme 2 in tumor growth and tumor-associated angiogenesis in non-small cell lung cancer.

Oncol Rep 2010 Apr;23(4):941-8

Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China.

Angiotensin II (AngII) is a multifunctional bioactive peptide and previous studies have shown that the renin-angiotensin system (RAS) of both host and tumor are important in tumor growth and angiogenesis in lung cancer. Angiotensin-converting enzyme 2 (ACE2) is a newly identified component of RAS, with 42% amino acid homology to ACE. However, the expression and function of ACE2 in non-small cell lung cancer (NSCLC) are still unclear. In the present study, we analyzed ACE2 expression in NSCLC tissue by Western blot analysis and immunohistochemistry. AngII concentrations in the tissue homogenate were also detected using radio-immunoassay. We also examined the function of ACE2 by transducing A549 cells with MSCV-ACE2. We have shown for the first time that ACE2 expression decreased in NSCLC tissue in which AngII was higher than the matching non-malignant tissues. A concentration of 10(-6) mol/l of AngII significantly increased expression of vascular endothelial growth factor a (VEGFa) and AT1-R and decreased ACE2 expression. We also found that overexpression of ACE2 may have a protective effect by inhibiting cell growth and VEGFa production in vitro. ACE2 may become a target of novel strategies to treat NSCLC.
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April 2010