Publications by authors named "Shumei Yan"

29 Publications

  • Page 1 of 1

Inhibin βA is an independent prognostic factor that promotes invasion via Hippo signaling in non‑small cell lung cancer.

Mol Med Rep 2021 11 10;24(5). Epub 2021 Sep 10.

Department of Pathology, The First Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110010, P.R. China.

Inhibin βA (INHBA) serves a prognostic and tumor‑promoting role in numerous types of cancer. The present study aimed to determine the clinical significance of INHBA in non‑small cell lung cancer (NSCLC) and the mechanisms underlying its potential tumor‑promoting effect. INHBA expression was detected in clinical NSCLC samples using immunohistochemistry. loss‑ and gain‑of‑function studies were performed to determine the effects of INHBA on NSCLC invasion. In addition, protein and mRNA expression levels of INHBA, yes‑associated protein (YAP), large tumor suppressor 1/2 kinase (LATS1/2), connective tissue growth factor, cysteine rich angiogenic inducer 61 and Merlin were assessed using western blotting and reverse transcription‑quantitative PCR, respectively, to investigate the mechanism by which INHBA may affect the invasion of NSCLC. The present study revealed that INHBA was significantly upregulated in 238 clinical NSCLC samples compared with its expression levels in paired adjacent non‑cancerous tissues, and in metastatic nodules compared with in primary tumors. Notably, high INHBA expression was statistically associated with clinicopathological features, including poor differentiation and advanced tumor stage. INHBA positivity was statistically related to decreased 5‑year overall survival, for which INHBA was an independent prognostic factor. Furthermore, INHBA promoted NSCLC invasion . In NSCLC, INHBA expression was associated with the nuclear levels of YAP and INHBA overexpression enhanced the invasive abilities of NSCLC cells via inhibiting the Hippo pathway. Mechanistically, INHBA inhibited l LATS1/2 phosphorylation and induced YAP nuclear translocation by downregulating the protein expression levels of Merlin. In conclusion, INHBA may negatively regulate the Hippo pathway to act as a tumor promotor, and could represent a marker of prognosis in NSCLC.
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http://dx.doi.org/10.3892/mmr.2021.12429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441965PMC
November 2021

Circular RNA circKIF4A facilitates the malignant progression and suppresses ferroptosis by sponging miR-1231 and upregulating GPX4 in papillary thyroid cancer.

Aging (Albany NY) 2021 06 21;13(12):16500-16512. Epub 2021 Jun 21.

Department of Head and Neck, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.

Circular RNAs (circRNAs) are one type of non-coding RNA. They act as important role in regulating various biological processes in the malignant progression. But we don't clearly know the specific mechanism of the majority circRNAs in papillary thyroid tumor progression. In the current study, we explored circKIF4A and the result showed that it had high expression in papillary thyroid cancer. The functions of circKIF4A were explored by CCK-8, transwell, and mouse xenograft experiments. Knockdown of circKIF4A could suppress papillary thyroid cell growth and migration. In addition, RIP assays and dual luciferase vector reporter assays were further conducted. Our consequence showed circKIF4A facilitated the malignant progress of papillary thyroid tumor by sponging miR-1231 and upregulating GPX4 expression. In conclusion, our study proved that circKIF4A-miR-1231-GPX4 axis played a vital role in cancer proliferation and ferroptosis by competing endogenous RNAs. Therefore, targeting circKIF4A is very likely to be a potential method for treatment of papillary thyroid cancer in the future.
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http://dx.doi.org/10.18632/aging.203172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266339PMC
June 2021

The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι.

Proc Natl Acad Sci U S A 2021 06;118(23)

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China;

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has claimed over 2 million lives worldwide. Although the genetic sequences of SARS-CoV and SARS-CoV-2 have high homology, the clinical and pathological characteristics of COVID-19 differ significantly from those of SARS. How and whether SARS-CoV-2 evades (cellular) immune surveillance requires further elucidation. In this study, we show that SARS-CoV-2 infection leads to major histocompability complex class Ι (MHC-Ι) down-regulation both in vitro and in vivo. The viral protein encoded by open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all viral proteins, directly interacts with MHC-Ι molecules and mediates their down-regulation. In ORF8-expressing cells, MHC-Ι molecules are selectively targeted for lysosomal degradation via autophagy. Thus, SARS-CoV-2-infected cells are much less sensitive to lysis by cytotoxic T lymphocytes. Because ORF8 protein impairs the antigen presentation system, inhibition of ORF8 could be a strategy to improve immune surveillance.
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http://dx.doi.org/10.1073/pnas.2024202118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201919PMC
June 2021

Efficacy and Safety of Bivalirudin During Percutaneous Coronary Intervention in Chronic Total Occlusion: A Retrospective Study.

Clin Ther 2021 05 31;43(5):844-851. Epub 2021 Mar 31.

Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address:

Purpose: Bivalirudin as a thrombin inhibitor is proven to have a low risk of bleeding during percutaneous coronary intervention (PCI). Some evidence indicates comparable effectiveness and safety between bivalirudin and unfractionated heparin (UFH). Although bivalirudin during PCI offers more clinical and safety benefits to patients with chronic total occlusion (CTO), mostly via radial access, this has not been confirmed. The objective of this study was to examine the efficacy and safety of bivalirudin during percutaneous coronary intervention (PCI) in patients with CTO.

Methods: This trial used a retrospective cohort study design. Medical information from 736 patients with CTO who underwent PCI with bivalirudin or UFH at the First Affiliated Hospital of Zhengzhou University from July 2019 to September 2020 was extracted and analyzed. The primary end point was the 30-day incidence of net adverse clinical events (NACEs), and the secondary end point was the major adverse cardiovascular events (MACEs), which were related to safety and efficacy, respectively. Other end points incorporated each component of the primary outcome, target vessel revascularization, and stent thrombosis. Clinical and procedural characteristics at baseline were adjusted by using a logistic regression model.

Findings: Overall, 71.5% of patients with CTO used the radial approach. Both groups exhibited nonsignificant differences in the majority of baseline characteristics. The bivalirudin group was associated with a significant reduction in NACEs (12.9% vs 21.5%; P = 0.002) and major bleeding (2.5% vs 8.0%; P = 0.001) versus the UFH group at the end of the 30-day follow-up. The incidence of MACEs, myocardial infarction, death, stroke, stent thrombosis, and target vessel revascularization did not differ significantly between the 2 groups. Moreover, the bivalirudin group also reported a lower incidence of NACEs in the prespecified subgroups.

Implications: Bivalirudin exhibited comparative efficacy but superior safety compared with UFH among patients with CTO undergoing PCI. Chinese Clinical Trial Registry: ChiCTR2000034771.
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http://dx.doi.org/10.1016/j.clinthera.2021.03.004DOI Listing
May 2021

Development of the C12Im-Cl-assisted method for rapid sample preparation in proteomic application.

Anal Methods 2021 02 25;13(6):776-781. Epub 2021 Jan 25.

Beijing Key Laboratory of Environmental and Viral Oncology, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China.

Chromatography and mass spectrometry (MS) techniques have greatly improved the power of proteomic analyses. However, sample processing methods used prior to MS, including protein extraction and digestion, remain bottlenecks in the large-scale clinical application of proteomics. Ionic liquids, composed entirely of ions, have high solubility in various solvents. In this study, the effects of the cationic surfactant 1-dodecyl-3-methylimidazolium chloride (C12Im-Cl) on protein digestion were evaluated for clinical proteomic applications. C12Im-Cl was compatible with trypsin and reduced the protein digestion time from 16 h to 1 h. Residual C12Im-Cl was easily removed with a strong anion exchange membrane before MS. We evaluated the performance of C12Im-Cl extraction and rapid protein digestion using formalin-fixed paraffin-embedded liver cancer tissues. The number of proteins and peptides identified was nearly equal to that identified by the traditional filter-aided sample preparation method (2705 vs. 2739 and 16 682 vs. 17 214). In general, the C12Im-Cl-aided rapid sample preparation method is promising for proteomic applications.
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http://dx.doi.org/10.1039/d0ay02079fDOI Listing
February 2021

High expression of eIF4A2 is associated with a poor prognosis in esophageal squamous cell carcinoma.

Oncol Lett 2020 Nov 31;20(5):177. Epub 2020 Aug 31.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.

Eukaryotic initiation factor 4A-II (eIF4A2) is an ATP-dependent RNA helicase involved in mRNA translation. Abnormal expression of eIF4A2 has been reported as a prognostic factor in different types of cancer. However, little is known regarding the function of eIF4A2 in esophageal squamous cell carcinoma (ESCC). In the present study, 253 samples were collected from patients diagnosed with ESCC, and the expression of eIF4A2 was detected by immunohistochemical staining. The clinicopathological and prognostic significance of eIF4A2 expression in ESCC were then statistically analyzed. The results demonstrated that eIF4A2 was specifically localized to the cytoplasm. Kaplan-Meier analysis also revealed that eIF4A2 expression was associated with the clinical prognosis of patients with ESCC. The median disease-free and overall survival times were 40 and 48 months for patients with low eIF4A2 expression, compared with 16 and 25 months in the high eIF4A2 expression group, respectively. In conclusion, high expression levels of eIF4A2 are associated with a poor prognosis and may be used as a potential prognostic indicator in patients with ESCC.
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http://dx.doi.org/10.3892/ol.2020.12038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471732PMC
November 2020

Maize pentatricopeptide repeat protein DEK53 is required for mitochondrial RNA editing at multiple sites and seed development.

J Exp Bot 2020 10;71(20):6246-6261

State Key Laboratory of Plant Physiology and Biochemistry, National Maize Improvement Center, Beijing Key Laboratory of Crop Genetic Improvement, Joint International Research Laboratory of Crop Molecular Breeding, College of Agronomy and Biotechnology, China Agricultural University, Beijing, China.

Pentatricopeptide repeat (PPR) proteins were identified as site-specific recognition factors for RNA editing in plant mitochondria and plastids. In this study, we characterized maize (Zea mays) kernel mutant defective kernel 53 (dek53), which has an embryo lethal and collapsed endosperm phenotype. Dek53 encodes an E-subgroup PPR protein, which possesses a short PLS repeat region of only seven repeats. Subcellular localization analysis indicated that DEK53 is localized in the mitochondrion. Strand- and transcript-specific RNA-seq analysis showed that the dek53 mutation affected C-to-U RNA editing at more than 60 mitochondrial C targets. Biochemical analysis of mitochondrial protein complexes revealed a significant reduction in the assembly of mitochondrial complex III in dek53. Transmission electron microscopic examination showed severe morphological defects of mitochondria in dek53 endosperm cells. In addition, yeast two-hybrid and luciferase complementation imaging assays indicated that DEK53 can interact with the mitochondrion-targeted non-PPR RNA editing factor ZmMORF1, suggesting that DEK53 might be a functional component of the organellar RNA editosome.
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http://dx.doi.org/10.1093/jxb/eraa348DOI Listing
October 2020

High expression of RABL6 promotes cell proliferation and predicts poor prognosis in esophageal squamous cell carcinoma.

BMC Cancer 2020 Jun 29;20(1):602. Epub 2020 Jun 29.

Department of Thoracic Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People's Republic of China.

Background: Esophageal squamous cell carcinoma (ESCC) is a common malignant carcinoma of digestive system with high mortality. RAB, member RAS oncogene family like 6 (RABL6), a member of the RAS subfamily, has been reported as an important molecule in several cancers. However, its potential role in ESCC still remains unclear.

Methods: RABL6 mRNA expression was detected in 93 frozen ESCC samples using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Immunohistochemistry was applied to evaluate the RABL6 expression in tissue microarray containing 171 pairs of ESCC tissues and paired para-cancerous tissues. We evaluated RABL6 expression and its correlation with clinicopathological characteristics and survival. Subsequently, the impact of RABL6 knockdown on the ability of cell proliferation, apoptosis, migration and epithelial-mesenchymal transition (EMT) of ESCC cells was investigated by MTS, Focus formation, flow cytometry, Transwell assays, qRT-PCR, western blot, inverted microscope observation and phalloidin staining, respectively.

Results: Compared to paired para-cancerous tissues, RABL6 was highly expressed in ESCC. The RABL6 high-expression was associated with worse prognosis. We also revealed silencing of RABL6 caused inhibition of cell proliferation, invasion and migration. Further experiments demonstrated that knockdown of RABL6 suppressed the aggressive biological activities of ESCC by suppressing EMT in ESCC cells.

Conclusions: RABL6 functions as a tumor oncogene in ESCC. It would be a potential biomarker predicting prognosis, and a novelty target for ESCC therapy.
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http://dx.doi.org/10.1186/s12885-020-07068-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325041PMC
June 2020

Constant expression of somatostatin receptor 2a in minute pulmonary meningothelial-like nodules.

J Clin Pathol 2019 Aug 17;72(8):525-528. Epub 2019 Jun 17.

Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China

Aims: Although ultrastructural studies showed that minute pulmonary meningothelial-like nodules (MPMNs) cells closely resembled meningothelial cells, their immunophenotype has not been well characterised, partly due to their rarity.

Methods: Somatostatin receptor 2a (SSTR2a) and other markers of meningioma, including epithelial membrane antigen (EMA), progesterone receptor (PR) and S100, were analysed retrospectively in 19 MPMN cases from two institutions in China.

Results: The median age of patients with MPMNs was 62.5 years (32-73 years), with a male-to-female ratio of 1:8.5. Most (15/19) patients with MPMNs had coexisting diseases, including adenocarcinomas (12 cases), bronchiectasis (1 case) and tuberculosis (2 cases). Just over half of the cases (10/19) were multifocal lesions (2-5 lesions). An additional 53 cases with 123 lesions from the literature were reviewed with reported immunophenotype information. In total, 162 lesions were included in the analysis. The size of nodules was 1-4 mm. All MPMN lesions (39/39) in the 19 cases showed strong and diffuse cytoplasmic expression of SSTR2a. The expression rate of SSTR2a was higher than that of conventional markers of meningioma, including EMA (86/138), PR (32/68) and S100 (1/125).

Conclusions: Our observations expand the spectrum of recognised SSTR2a-positive lesions and once again demonstrated that MPMNs show immunohistochemical characteristics similar to meningothelial cells.
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http://dx.doi.org/10.1136/jclinpath-2019-205913DOI Listing
August 2019

Incidental lymphoma in lymph node dissection for carcinoma in the abdominopelvic cavity: a single-institution experience.

Virchows Arch 2019 Sep 2;475(3):365-372. Epub 2019 May 2.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China.

Incidental detection of lymphoma in lymph node (LN) dissection for carcinoma is extremely rare. The occurrence and clinicopathological features of this rare condition have not been characterised. The medical records of 11,889 consecutive patients who underwent LN dissection for carcinoma in the abdominopelvic cavity were retrospectively reviewed. Among these patients, 11 had lymphomas detected in LN dissections and 7 had no previous history of lymphoma, representing an incidental detection rate of 0.06% (7/11889). The patients had a median age of 63 years (range, 48-69 years), and the male-to-female ratio was 1:2.5. The sites and histological types of the carcinoma were as follows: adenocarcinoma of the sigmoid colon (2 cases), endometrioid adenocarcinoma of the endometrium (2 cases), squamous carcinoma of the uterine cervix (1 case), adenocarcinoma of the stomach (1 case), and adenocarcinoma of the rectum (1 case). All incidental lymphoma cases (100%, 7/7) were low-grade B cell non-Hodgkin lymphoma (B-NHL), including 5 cases of follicular lymphoma (grades 1-2) and 2 cases of small lymphocytic lymphoma. The median follow-up interval was 39 months (5-65 months). All the patients were alive at the end of the follow-up period. Low-grade B-NHL can be incidentally detected during LN dissection for carcinoma in the abdominopelvic cavity. The subtype of incidental lymphoma is likely related to the epidemiology of lymphoma classes in the corresponding area. We should be aware of simultaneous occurrence of incidental lymphoma during lymphadenectomy for carcinoma.
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http://dx.doi.org/10.1007/s00428-019-02578-wDOI Listing
September 2019

High-dose Methotrexate plus temozolomide with or without rituximab in patients with untreated primary central nervous system lymphoma: A retrospective study from China.

Cancer Med 2019 04 1;8(4):1359-1367. Epub 2019 Mar 1.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.

The purpose of this retrospective study was to compare the efficacy and toxicity of high-dose methotrexate plus temozolomide (MT regimen) and rituximab plus MT (RMT regimen) in patients with untreated primary central nervous system lymphoma (PCNSL). A total of 62 patients with untreated PCNSL were enrolled between January 2005 and December 2015, with the median age of 53.5 years (range 29-77).In this study, 32 patients received RMT as induction therapy, and 30 received MT. Objective responses were noted in 93.7% of the patients in the RMT group and in 69.0% of the patients in the MT group (P = 0.018), while complete responses were noted in 53.2% of the patients in the RMT group and 27.6% of the patients in the MT group (P < 0.001). The 2- and 5-year PFS rates were 81.3% and 53.3%, respectively, for the RMT group and 46.5% and 29.1%, respectively, for the MT group (P = 0.019). The 2- and 5-year overall survival (OS) rates were 82.3% and 82.3%, respectively, for the RMT group and 65.7% and 50.0%, respectively, for the MT group (P = 0.015). Multivariate analyses showed that therapeutic regimen (RMT vs MT) was an independent prognostic factor for PFS and OS. Our encouraging results suggest that the RMT regimen may be a feasible and safe therapeutic approach for first-line treatment of PCNSL.
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http://dx.doi.org/10.1002/cam4.1906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488123PMC
April 2019

High CEP55 expression is associated with poor prognosis in non-small-cell lung cancer.

Onco Targets Ther 2018 17;11:4979-4990. Epub 2018 Aug 17.

Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China,

Objectives: Lung cancer is the most common and lethal malignancy worldwide. CEP55 was found to be overexpressed in multiple types of cancer. However, the expression pattern of CEP55 and its clinical significance in non-small-cell lung carcinoma (NSCLC) have not been investigated by immunohistochemistry.

Materials And Methods: In this study, we analyzed 203 primary NSCLC specimens from Sun Yat-Sen University Cancer Center to investigate the clinical role of CEP55 in lung cancer. Tissue microarray was successfully generated for immunohistochemical evaluation. The correlation between CEP55 expression and clinical characteristics and survival was analyzed statistically. The predictive effect of CEP55 and APOBEC3B (AP3B) coexpression in lung cancer patients' prognosis was evaluated.

Results: We found that the CEP55 expression was commonly elevated in NSCLC tissues and overexpression of CEP55 was correlated with unfavorable prognosis in the patients with NSCLC. Furthermore, the combination of CEP55 and AP3B expression was significantly predictive of clinical outcome in all NSCLC patients.

Conclusion: CEP55 may act as a useful and novel prognostic biomarker for NSCLC. Further studies into the mechanism of CEP55 are warranted.
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http://dx.doi.org/10.2147/OTT.S165750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103653PMC
August 2018

INHBA upregulation correlates with poorer prognosis in patients with esophageal squamous cell carcinoma.

Cancer Manag Res 2018 18;10:1585-1596. Epub 2018 Jun 18.

Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Purpose: INHBA, which encodes a member of the TGF-beta superfamily of proteins, has been identified to play a critical role in different types of cancer. However, its clinical significance in esophageal squamous cell carcinoma (ESCC) has never been reported.

Patients And Methods: In this study, we collected 239 ESCC paraffin-embedded specimens and measured the expression of INHBA with immunohistochemistry (IHC). The clinical and prognostic significance of INHBA expression was statistically analyzed. What is more, we conducted a meta-analysis to study the prognostic value of INHBA expression in multiple types of solid tumors.

Results: The results showed that INHBA expression was observed predominantly in the cytoplasm of cells in the ESCC specimens. INHBA expression was closely correlated with N categories (=0.026). Kaplan-Meier analysis showed that ESCC patients in the low INHBA expression subgroup had significantly better prognosis than those with high INHBA level. Subgroup analysis revealed that INHBA distinguished the disease-free survival (DFS) and overall survival (OS) when patients were stratified by TNM stage status and N status. Multivariate analysis results suggested that INHBA expression was an independent factor that affected OS (HR =1.679, =0.022) and DFS (HR =1.715, =0.017). In the meta-analysis, six papers with 1321 patients were included and patients with high INHBA level had worse prognosis than patients with low INHBA level (HR 2.50, 95% CI 1.75-3.57, <0.0001).

Conclusion: High INHBA level predicts poor prognosis in ESCC and other solid tumors. More studies are required to elucidate the role of INHBA and its clinical application in cancer settings.
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http://dx.doi.org/10.2147/CMAR.S160186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014728PMC
June 2018

OPAQUE11 Is a Central Hub of the Regulatory Network for Maize Endosperm Development and Nutrient Metabolism.

Plant Cell 2018 02 7;30(2):375-396. Epub 2018 Feb 7.

Shanghai Key Laboratory of Bio-Energy Crops, Plant Science Center, School of Life Sciences, Shanghai University, Shanghai 200444, China

Maize () endosperm is a primary tissue for nutrient storage and is highly differentiated during development. However, the regulatory networks of endosperm development and nutrient metabolism remain largely unknown. Maize () is a classic seed mutant with a small and opaque endosperm showing decreased starch and protein accumulation. We cloned and found that it encodes an endosperm-specific bHLH transcription factor (TF). Loss of function of O11 significantly affected transcription of carbohydrate/amino acid metabolism and stress response genes. Genome-wide binding site analysis revealed 9885 O11 binding sites distributed over 6033 genes. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with RNA sequencing (RNA-seq) assays, we identified 259 O11-modulated target genes. O11 was found to directly regulate key TFs in endosperm development (NKD2 and ZmDOF3) and nutrient metabolism (O2 and PBF). Moreover, O11 directly regulates cyPPDKs and multiple carbohydrate metabolic enzymes. O11 is an activator of , suggesting its regulatory function through the MAPK pathway in endosperm development. Many stress-response genes are also direct targets of O11. In addition, 11 O11-interacting proteins were identified, including , which coregulates stress response targets and with O11. Therefore, this study reveals an endosperm regulatory network centered around O11, which coordinates endosperm development, metabolism and stress responses.
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http://dx.doi.org/10.1105/tpc.17.00616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868688PMC
February 2018

Preoperative prediction nomogram based on primary tumor miRNAs signature and clinical-related features for axillary lymph node metastasis in early-stage invasive breast cancer.

Int J Cancer 2018 05 12;142(9):1901-1910. Epub 2018 Jan 12.

Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.

More than half patients who undergo axillary lymph node (ALN) surgery are ALN negative in early-stage invasive breast cancer (EIBC). Thus, to avoid excessive treatment, we aim to establish and validate a novel nomogram model for the preoperative diagnosis of ALN status in patients with EIBC. In total, 864 patients with EIBC from two independent centers were enrolled in our study. For the discovery set, miRNAs expression profiling with functional roles in ALN metastasis was discovered by microarray analysis and validated by quantitative polymerase chain reaction (PCR). For the training and validation cohorts, we used PCR to quantify miRNAs expression in a model development cohort and assessed miRNAs signature in an internal validation cohort and external independent validation cohort. Multivariable logistic regression analyses were used to establish a nomogram model for the likelihood of ALN metastasis from miRNAs signature and clinical variables. A signature of nine-miRNA was significantly associated with ALN status. The predictive ability of our nomogram that included miRNAs signature and clinical-related variables (age, tumor size, tumor location and axillary ultrasound-reported ALN status) was significantly greater than a model that only considered clinical-related factors (concordance index: 0.856, 0.796) and also performed well in the two validation cohorts (concordance index: 0.841, 0.747). Our nomogram is a reliable prediction method that can be conveniently used to preoperatively predict ALN status in patients with EIBC. Therefore, after further confirmation in prospective and multicenter clinical trial, omission of axillary surgery may be feasible for some patients with EIBC in the future.
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http://dx.doi.org/10.1002/ijc.31208DOI Listing
May 2018

WWC2 is an independent prognostic factor and prevents invasion via Hippo signalling in hepatocellular carcinoma.

J Cell Mol Med 2017 Dec 16;21(12):3718-3729. Epub 2017 Aug 16.

Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.

WWC family proteins negatively regulate HEK293 cell proliferation and organ growth by suppressing the transcriptional activity of Yes-associated protein (YAP), a major effector of the Hippo pathway. The function of the scaffolding protein WWC1 (also called KIBRA) has been intensively studied in cells and animal models. However, the expression and clinicopathologic significance of WWC2 in cancer are poorly characterized. This study aimed to clarify the biological function and mechanism of action of WWC2 in hepatocellular carcinoma (HCC). Retrospective analysis revealed WWC2 was significantly down-regulated in 95 clinical HCC tissues compared to the paired adjacent non-cancerous tissues. Moreover, loss of WWC2 expression was significantly associated with advanced clinicopathological features, including venous infiltration, larger tumour size and advanced TNM stage. Positive WWC2 expression was associated with significantly better 5-year overall survival, and WWC2 was an independent prognostic factor for overall survival in HCC. Moreover, we confirmed WWC2 inhibits HCC cell invasive ability in vitro. Elevated YAP expression was also observed in the same cohort of HCC tissues. Pearson's correlation coefficient analysis indicated WWC2 expression correlated inversely with nuclear YAP protein expression in HCC. Mechanistically, we confirmed overexpression of WWC2 suppresses the invasive and metastatic potential of HCC cells by activating large tumour suppressor 1 and 2 kinases (LATS1/2), which in turn phosphorylates the transcriptional co-activator YAP. Overall, this study indicates WWC2 functions as a tumour suppressor by negatively regulating the Hippo signalling pathway and may serve as a prognostic marker in HCC.
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http://dx.doi.org/10.1111/jcmm.13281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706493PMC
December 2017

Serum EBV EA-IgA and VCA-IgA antibodies can be used for risk group stratification and prognostic prediction in extranodal NK/T cell lymphoma: 24-year experience at a single institution.

Ann Hematol 2017 Aug 27;96(8):1331-1342. Epub 2017 May 27.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China.

Although extranodal NK/T cell lymphoma (ENKTCL) is consistently associated with Epstein-Barr virus (EBV) infection, the manifestation and prognostic value of serum EBV antibodies still remain unknown. One hundred and forty-one patients with ENKTCL were evaluated for serum EBV EA-IgA and VCA-IgA antibodies levels in the past 24 years in our institution. Their correlation with clinicopathological features, plasma EBV DNA load, and patients' outcomes was analyzed. EBV EA-IgA ≥1:10 and VCA-IgA ≥1:160 were found in 18.4 and 16.3% of patients, respectively. They correlated with adverse ENKTCL profile and inferior overall survival (OS) and progression-free survival (PFS). EA-IgA ≥1:10 was an independent prognostic factor on OS (RR = 2.276, p = 0.008) and associated with lower complete response (CR) rate (34.8 vs 70.6%, p = 0.001) and higher relapse rate in CR patients (62.5 vs 34.7%, p = 0.016). In subgroup analysis, both EA-IgA ≥1:10 and VCA-IgA ≥1:160 significantly correlated with inferior OS and PFS in patients with stage I/II, IPI score 0-1, plasma EBV DNA (+), and CR. Patients with plasma EBV DNA (+) and EA-IgA ≥1:10 (or VCA-IgA ≥1:160) had significantly shorter periods of OS and PFS in comparison with other corresponding groups. Elevated serum EBV EA-IgA and VCA-IgA levels were related to adverse ENKTCL profile and correlated with poor treatment response, early relapse, and poor prognosis in patients with ENKTCL. These findings provide convincing evidence for the use of serum EBV EA-IgA and VCA-IgA antibodies for risk group stratification and prognostic prediction in ENKTCL.
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http://dx.doi.org/10.1007/s00277-017-3013-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486802PMC
August 2017

The Role of GOLPH3L in the Prognosis and NACT response in Cervical Cancer.

J Cancer 2017 10;8(3):443-454. Epub 2017 Feb 10.

Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510080, China.

We previously reported GOLPH3L is a novel oncogene associated with ovarian cancer. The role of GOLPH3L in cervical cancer and its cellular functions has not been determined. This study investigated clinical significance of GOLPH3L and potential proteins and pathways associated with GOLPH3L in cervical squamous cell carcinoma. Immunohistochemistry and western blot were used to examine the expression of GOLPH3L in cervical squamous cell carcinoma tissue specimens and adjacent non-cancerous tissues. The clinical and prognostic significance of GOLPH3L expression was statistically analyzed. Cell proliferation rate, cell cycle progression, apoptosis and cisplatin response in GOLPH3L silenced SiHa and HeLa cells were also examined. Phospho-antibody array was used to identify changes in protein phosphorylation and the corresponding signaling pathways associated with these changes. GOLPH3L overexpressed in cervical cancer tissue specimens compared with normal adjacent non-cancerous tissues. Increased GOLPH3L expression was associated with FIGO staging (P=0.033), cervical stromal invasion (P=0.037), cervical canal stromal invasion (P=0.027), lymph node metastasis (P=0.016) and positive surgical margins (P=0.015). Patients with lower expression of GOLPH3L demonstrated longer progression-free survival and overall survival compared with those with higher expression. The tissue samples from patients who poorly responded to neoadjuvant chemotherapy (NACT) exhibited increased GOLPH3L expression levels compared with tissue samples from patients who achieved a pathologic complete response (pCR). Patients with lower GOLPH3L expression level, poorer tumor differentiation, shorter NACT treatment intervals and smaller tumor sizes were more likely to achieve a pCR after NACT. Knockdown GOLPH3L in cells was associated with an induction of cell cycle arrest, increased apoptosis and cisplatin sensitivity, and a reduction in cellular viability. Phospho-antibody array suggested GOLPH3L plays a role in mediating cell cycle arrest. This study provides a potential biomarker for predicting prognosis and NACT response in patients with cervical squamous cell carcinoma. The functional role of GOLPH3L in cervical cancer merits further investigation.
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http://dx.doi.org/10.7150/jca.17096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332896PMC
February 2017

Dacomitinib, a new pan-EGFR inhibitor, is effective in killing ovarian cancer cells.

Discov Med 2016 11;22(122):297-309

Department of Bioengineering and Biotechnology, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian 361021, China.

Objective: Aberrant epidermal growth factor receptor (EGFR) is involved in a variety of cancers and its inhibitors have been studied for over a decade. We aim to investigate the effects of dacomitinib, a second generation pan-EGFR inhibitor, on ovarian cancer cells.

Methods: By immunohistochemistry, we studied the clinical significance of EGFR expression in epithelial ovarian cancer (EOC). The correlations between EGFR expression and the clinicopathological variables of patients with EOC were assessed using Pearson's X2 test. Kaplan-Meier analysis was used to compare the postoperative survival between groups of patients with EOC with varying levels of EGFR expression. MTT, caspase assay, cell apoptosis analysis, autophagy analysis, cell cycle analysis, and western blotting were used to investigate various effects of dacomitinib in cell proliferation, apoptosis, and associated molecular pathways.

Results: High expression of EGFR was found to be associated with poor prognosis of patients with EOC. EGFR, P-AKT, and P-ERK were inhibited after treatment of dacomitinib in both SKOV3 and OV4 cells. Activations of caspase activities, apoptosis, and autophagy were also observed and confirmed by western blot: caspase 9, LC3, and Bax levels were elevated, while Bcl-2 and Bcl-xl were down-regulated. The percentage of cancer cells in the S and G2 phases of the cell cycle significantly decreased after treatment. Cdk1 and Cdk2 protein levels declined after dacomitinib treatment; epithelial-mesenchymal transition (EMT) was inhibited, which was confirmed by observing E-cadherin, N-cadherin, and slug inhibition. Additionally, dacomitinib significantly increased chemotherapy sensitivity in chemotherapeutic resistant ovarian cell lines, C13 and 2780CP.

Conclusion: Our data showed that increased expression of EGFR is associated with poor prognosis of patients with EOC and dacomitinib may act as a novel, useful chemotherapy drug. Further studies are warranted.
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November 2016

Growth hormone-releasing hormone receptor antagonists inhibit human gastric cancer through downregulation of PAK1-STAT3/NF-κB signaling.

Proc Natl Acad Sci U S A 2016 12 7;113(51):14745-14750. Epub 2016 Dec 7.

Cancer Research Center, Shantou University Medical College, Shantou 515041, China;

Gastric cancer (GC) ranks as the fourth most frequent in incidence and second in mortality among all cancers worldwide. The development of effective treatment approaches is an urgent requirement. Growth hormone-releasing hormone (GHRH) and GHRH receptor (GHRH-R) have been found to be present in a variety of tumoral tissues and cell lines. Therefore the inhibition of GHRH-R was proposed as a promising approach for the treatment of these cancers. However, little is known about GHRH-R and the relevant therapy in human GC. By survival analyses of multiple cohorts of GC patients, we identified that increased GHRH-R in tumor specimens correlates with poor survival and is an independent predictor of patient prognosis. We next showed that MIA-602, a highly potent GHRH-R antagonist, effectively inhibited GC growth in cultured cells. Further, this inhibitory effect was verified in multiple models of human GC cell lines xenografted into nude mice. Mechanistically, GHRH-R antagonists target GHRH-R and down-regulate the p21-activated kinase 1 (PAK1)-mediated signal transducer and activator of transcription 3 (STAT3)/nuclear factor-κB (NF-κB) inflammatory pathway. Overall, our studies establish GHRH-R as a potential molecular target in human GC and suggest treatment with GHRH-R antagonist as a promising therapeutic intervention for this cancer.
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http://dx.doi.org/10.1073/pnas.1618582114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187693PMC
December 2016

Maize opaque10 Encodes a Cereal-Specific Protein That Is Essential for the Proper Distribution of Zeins in Endosperm Protein Bodies.

PLoS Genet 2016 08 19;12(8):e1006270. Epub 2016 Aug 19.

Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, China.

Cereal storage proteins are major nitrogen sources for humans and livestock. Prolamins are the most abundant storage protein in most cereals. They are deposited into protein bodies (PBs) in seed endosperm. The inner structure and the storage mechanism for prolamin PBs is poorly understood. Maize opaque10 (o10) is a classic opaque endosperm mutant with misshapen PBs. Through positional cloning, we found that O10 encodes a novel cereal-specific PB protein. Its middle domain contains a seven-repeat sequence that is responsible for its dimerization. Its C terminus contains a transmembrane motif that is required for its ER localization and PB deposition. A cellular fractionation assay indicated that O10 is initially synthesized in the cytoplasm and then anchored to the ER and eventually deposited in the PB. O10 can interact with 19-kD and 22-kD α-zeins and 16-kD and 50-kD γ-zeins through its N-terminal domain. An immunolocalization assay indicated that O10 co-localizes with 16-kD γ-zein and 22-kD α-zein in PBs, forming a ring-shaped structure at the interface between the α-zein-rich core and the γ-zein-rich peripheral region. The loss of O10 function disrupts this ring-shaped distribution of 22-kD and 16-kD zeins, resulting in misshapen PBs. These results showed that O10, as a newly evolved PB protein, is essential for the ring-shaped distribution of 22-kD and 16-kD zeins and controls PB morphology in maize endosperm.
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http://dx.doi.org/10.1371/journal.pgen.1006270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991801PMC
August 2016

Reduced Expression of FADS1 Predicts Worse Prognosis in Non-Small-Cell Lung Cancer.

J Cancer 2016 18;7(10):1226-32. Epub 2016 Jun 18.

1. Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao 266000, P.R. China;

Objective: Fatty acid desaturase 1 is a member of the fatty acid desaturase, which is related to a number of diseases. However, its role in cancers remains unclear. This study was to explore the clinical importance of FADS1 expression in non-small-cell lung cancer (NSCLC).

Materials And Methods: Immunochemistry was used to evaluate FADS1 expressions in 216 paraffin-embedded specimens. The expression of FADS1 was divided into high and low groups. The clinical and prognostic significance of FADS1 expression was analyzed statistically by Kaplan-Meier estimate and Cox regression model.

Results: FADS1 overexpressed in normal bronchial mucosa compared with non-small-cell lung cancer. Reduced FADS1 expression was associated with tumor size (P=0.023) and histological grade (P<0.0001). Patients with lower expression of FADS1 had shorter overall survival and disease free survival (P=0.001 and P=0.002). Multivariate analysis showed FADS1 expression was an independent prognostic factor in NSCLC (P=0.011).

Conclusion: Reduced expression of FADS1 suggests pessimistic prognosis for NSCLC patients. Further studies are warranted.
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http://dx.doi.org/10.7150/jca.15403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4934030PMC
July 2016

TACC3 promotes colorectal cancer tumourigenesis and correlates with poor prognosis.

Oncotarget 2016 Jul;7(27):41885-41897

Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology and The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

Colorectal carcinoma (CRC) is a malignant epithelial tumour with tremendous invasion and metastatic capacity. Transforming acidic coiled-coil protein-3 (TACC3), a frequently aberrantly expressed oncogene, is an important biomarker in various human cancers. Our study aimed to investigate the expression and function of TACC3 in human CRC. We found that TACC3 was over-expressed at both the mRNA and protein levels in CRC cells and in biopsies of CRC tissues compared with normal controls as determined by qRT-PCR, western blot and immunohistochemical (IHC) staining assays. IHC staining of samples from 161 patients with CRC also revealed that TACC3 expression was significantly correlated with clinical stage (P = 0.045), T classification (P = 0.029) and M classification (P = 0.020). Multivariate analysis indicated that high TACC3 expression was an independent prognostic marker for CRC. Patients who had high TACC3 expression had significantly poorer overall survival (OS, P = 0.023) and disease-free survival (DFS, P = 0.019) compared to patients who had low TACC3 expression. Furthermore, TACC3 knockdown attenuated CRC cell proliferation, colony formation capability, migration and invasion capability, and tumourigenesis in nude mice; these properties were measured using a real-time cell analyser (RTCA), clonogenicity analysis, and transwell and xenograft assays, respectively. These data indicate that TACC3 promotes CRC progression and could be an independent prognostic factor and a potential therapeutic target for CRC.
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http://dx.doi.org/10.18632/oncotarget.9628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5173103PMC
July 2016

Increased APOBEC3B Predicts Worse Outcomes in Lung Cancer: A Comprehensive Retrospective Study.

J Cancer 2016 19;7(6):618-25. Epub 2016 Mar 19.

1. State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou City, Guangdong Province, P.R. China;; 2. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou City, Guangdong Province, P.R. China;

Lung cancer ranks as the most common and lethal malignancy in America and worldwide. APOBEC3B is a newly identified DNA cytosine deaminase, which is supposed to function as a major source of DNA mutation in many different tumors. In this study, we combine the data of online databases and two hundred and twenty-one primary non-small-cell lung carcinoma (NSCLC) specimens from Sun Yat-sen University Cancer Center to investigate, for the first time, the clinical role of APOBEC3B in lung cancer. We found that the APOBEC3 expression was commonly elevated in NSCLC tissues and overexpression of APOBEC3B was correlated with unfavorable prognosis of the patients with NSCLC. Furthermore, APOBEC3B expression was associated with nodal status, TNM staging and adjuvant chemotherapy of the patients with NSCLC. Further research is warranted.
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http://dx.doi.org/10.7150/jca.14030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829547PMC
April 2016

High expression of HEF1 predicts a poorer prognosis of hepatocellular carcinoma: A retrospective study.

Mol Clin Oncol 2016 Feb 11;4(2):159-165. Epub 2015 Dec 11.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.

Human enhancer of filamentation 1 (HEF1), a scaffold protein, is highly expressed in a variety of cancer types and is involved cancer cell growth, migration and invasion. The prognostic value of HEF1 in hepatocellular carcinoma (HCC) remains to be elucidated. The aim of the present study was to assess the association between the expression of HEF1, the clinical/pathological parameters and survival in HCC. In the present study, immunohistochemistry was performed to investigate the protein expression of HEF1 in 123 hepatocellular carcinoma tissues and their adjacent normal liver tissues. Spearman's rank correlation, Kaplan-Meier plots and Cox regression model were used to analyze the data. Overexpression of HEF1 protein was observed in HCC tissue when compared with their adjacent non-malignant liver tissue. High expression of HEF1 correlated with higher advanced tumor, node, metastasis (TNM) stage and vascular invasion (P<0.05). In univariate and multivariate analysis, the expression of HEF1 was identified as an independent prognostic factor in the 123 patients with HCC. In subgroup analysis, high expression of HEF1 correlated with a poorer prognosis in advanced (TNM III+IV) stages (P<0.05). These findings demonstrated the potential value of detecting the expression of HEF1 by immunohistochemistry as a prognostic biomarker and therapeutic target for patients with HCC.
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http://dx.doi.org/10.3892/mco.2015.707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733949PMC
February 2016

Programmed cell death ligand 1 (PD-L1) expression on gastric cancer and its relationship with clinicopathologic factors.

Int J Clin Exp Pathol 2015 1;8(9):11084-91. Epub 2015 Sep 1.

Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou 510060, China.

Background: Targeting the immune checkpoints in solid tumors becomes hot recently. Programmed cell death ligand 1 (PD-L1) is ligand for programmed death 1 (PD-1), which is known to negatively regulate T-cell activation. In the present study, we investigated the expression of PD-L1 in tumor specimens of gastric cancer and its relationships with clinicopathological variables and survival.

Methods: The expression of PD-L1 in 132 surgically resected specimens of stage II and III gastric cancer was evaluated by immunohistochemistry in microarray tissue.

Results: Expression of PD-L1 was observed in 50.8% (67/132) of gastric cancer tumor specimens. Patients whose tumor size over 5cm had a higher positive rate of PD-L1 expression. There was no relationship between the expression of PD-L1 and other clinicopathological variables including age, gender, clinical stage, location as well as histological differentiation. PD-L1 positive patients had significantly poorer survival than negative patients. The 5-year survival rates was 83.1% in those with PD-L1 negative patients and 50.7% for PD-L1 positive patients (P<0.001). The multivariate analysis indicated that both PD-L1 positive and Tumor-node-metastasis stage were independent prognostic factors in gastric cancer patients (P=0.001 and 0.025, respectively).

Conclusions: The expression of PD-L1 was found in half of stages II and III gastric cancer patients. Positive of PD-L1 expression indicated poor survival in Chinese stages II and III gastric adenocarcinoma patients. These results may provide the clue for immunotherapy in the adjuvant treatment setting of gastric cancer patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637642PMC
September 2016

Decreased expression of BRCA1-associated protein 1 predicts unfavorable survival in gastric adenocarcinoma.

Tumour Biol 2016 May 26;37(5):6125-33. Epub 2015 Nov 26.

State Key Laboratory of Oncology in South China, Department of Gastric and Pancreatic Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651, Dongfeng East Road, 510060, Guangzhou, Guangdong, People's Republic of China.

BRCA1-associated protein 1 (BAP1) has been reported as a novel tumor suppressor, while in gastric adenocarcinoma, the function of this protein was still await to be uncovered. Based on a large group of patients with gastric adenocarcinoma, our study aimed to have a further understanding about the correlation of BAP1 expression and patients' clinical outcomes. We performed quantitative PCR and Western blot to examine BAP1 expression in 38 cases of gastric adenocarcinoma samples and adjacent non-cancerous tissues. Immunochemistry was used to evaluate BAP1 expression in a large cohort of 474 paraffin-embedded specimens. The clinical and prognostic significance of BAP1 expression was statistically analyzed. Postoperative survival between groups was using Kaplan-Meier analysis. BAP1 was overexpressed in paracancerous normal mucosa compared with gastric cancer. Decreased BAP1 expression was associated with higher histologic grade (P = 0.044), tumor infiltration (P < 0.001), metastasis status (P = 0.023), and TNM stage (P < 0.001). Patients with low expression of BAP1 had shorter overall survival compared with those with high expression (P < 0.001). Patients' survival in stage N0 could be stratified by the expression of BAP1. Multivariate analysis showed that in gastric adenocarcinoma, BAP1 expressing level was an independent prognostic factor (RR = 0.575, P < 0.001). Decreased expression of BAP1 suggests pessimistic prognosis for gastric adenocarcinoma patients. Further studies are warranted.
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http://dx.doi.org/10.1007/s13277-015-3983-0DOI Listing
May 2016

[Analysis of mature T-cell and NK-cell lymphoma with CD30 expression based on latest WHO classification].

Zhonghua Bing Li Xue Za Zhi 2014 Aug;43(8):508-11

Department of Pathology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

Objective: To investigate the frequency of different types of mature T- and NK-cell lymphomas diagnosed in a 4-year period at Sun Yat-sen University Cancer Center, and to study baseline CD30 for potential anti-CD30 targeted therapy in mature T- and NK-cell lymphoma.

Methods: All cases of mature T- and NK-cell lymphoma diagnosed at Sun Yat-sen University Cancer Center from September 1, 2009 to August 31, 2013, were reviewed. Paraffin-blocks of available 164 consecutive cases were stained for CD30 immunohistochemistry using EnVision protocol.

Results: A total of 625 cases of mature T- and NK-cell lymphomas were diagnosed and the most common type was extranodal NK/T cell lymphoma (ENKTL), nasal type 319 (51.0%) cases, followed by angioimmunoblastic T-cell lymphoma (AITL) (119 cases, 19.0%), peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) (81 cases, 13.0%), and anaplastic large-cell lymphoma (ALCL), including 48 cases (7.7%) of systematic ALCL and 11 cases (1.8%) of primary cutaneous ALCL. Besides ALCL, ENKTL had the highest expression rate of CD30 among the 164 cases, with positivity observed in 41 cases (62.1%, 41/66). Only 1 case of PTCL-NOS was CD30 positive. CD30 was not expressed in all 28 cases of AITL and other rare types of mature T- and NK-cell lymphoma.

Conclusions: The frequency of different types of mature T- and NK-cell lymphoma encountered at Sun Yat-sen University Cancer Center was similar to that seen in other areas of China and other Asia countries. CD30 expression is different among several types of mature T- and NK-cell lymphoma. In addition to ALCL, ENKTL has the highest expression rate of CD30, which may be a candidate disease for anti-CD30 targeted therapy.
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August 2014

Prognostic significance of BRCA1-associated protein 1 in colorectal cancer.

Med Oncol 2013 Jun 23;30(2):541. Epub 2013 Mar 23.

State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, No 651, Dongfeng Road East, Guangzhou 510060, China.

Mutations of BRCA1-associated protein 1 (BAP1), a nuclear-localized deubiquitinating enzyme, had been documented in multiple human cancers. However, its role and clinical relevance in colorectal cancer is unknown. The purpose of this study was to reveal the prognostic significance of BAP1 in colorectal cancer. We performed quantitative PCR and Western blotting analyses to examine BAP1 expression in 8 cases of CRC tissues and matched adjacent non-cancerous tissues. And immunohistochemistry was used to evaluate BAP1 expression in archived 252 paraffin-embedded CRC specimens. We found that the mRNA and protein levels of BAP1 were down-regulated in 6 out of 8 cases of CRC tissues compared with their adjacent non-cancerous tissues. The BAP1 expression was closely correlated with age (p = 0.037), clinical stage (p = 0.001), T classification (p < 0.001), N classification (p < 0.001), and pathologic differentiation (p = 0.008) and histological type (p = 0.047) in CRC. The CRC patients with lower BAP1 expression survived shorter than those with higher BAP1 expression. Importantly, multivariate analysis demonstrated that BAP1 expression was an independent prognostic factor for CRC (p = 0.037). Collectively, we provide the first evidence that reduced BAP1 expression is associated with poor prognosis of CRC and BAP1 may serve as a novel prognostic biomarker for CRC.
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http://dx.doi.org/10.1007/s12032-013-0541-8DOI Listing
June 2013
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