[ENTPD5 gene is highly expressed in epithelial ovarian cancer: analysis based on Oncomine database and bioinformatics].

OBJECTIVE To investigate the expression of ENTPD5 in epithelial ovarian cancer and explore its clinical implications. OBJECTIVE The expression level of ENTPD5 in epithelial ovarian cancer was analyzed based on data from Oncomine and TCGA databases. The relationship between the expression level of ENTPD5 and clinical characteristics of the patients was analyzed using UALCAN database. Gene enrichment analysis (GSEA) was performed to explore the possible role of ENTPD5 in the occurrence and progression of epithelial ovarian cancer. CIBERSORT package was used to analyze the relationship between the expression of ENTPD5 and immune infiltration. The expression patterns of ENTPD5 were verified in 23 epithelial ovarian cancer tissues and 15 normal ovarian tissues using RT-qPCR and Western blotting; the expression of ENTPD5 protein was also detected immunohistochemically in 50 paraffin-embedded samples of epithelial ovarian cancer and 6 normal ovarian tissues. OBJECTIVE Analysis of Oncomine and TCGA databases showed that the expression of ENTPD5 was significantly higher in epithelial ovarian cancer tissues than in normal ovarian tissues (P < 0.05), and its expression level was negatively correlated with the survival rate of the patients (P < 0.05). Data from UALCAN database showed that the expression level of ENTPD5 was related with the age of patients. The results of GSEA suggested that ENTPD5 was involved in ABC transporter, WNT signaling pathway and insulin signaling, and the expression of ENTPD5 was negatively correlated with the contents of NK cells, mast cells and eosinophils (P < 0.05). In clinical samples of epithelial ovarian cancer tissues, the expression of ENTPD5 was significantly higher than that in normal ovarian tissues at both the mRNA (P < 0.01) and protein (P < 0.05) levels. The paraffinembedded samples also showed significantly higher expressions of ENTPD5 in epithelial ovarian cancer than in normal ovarian tissues (P < 0.05). OBJECTIVE ENTPD5 is highly expressed in epithelial ovarian cancer, which may promote the occurrence and progression of epithelial ovarian cancer by participating in multiple functional processes and cellular immune infiltration.

[1]  V. M. Neto,et al.  ABC transporters and the hallmarks of cancer: roles in cancer aggressiveness beyond multidrug resistance , 2020, Cancer biology & medicine.

[2]  M. Bednaříková,et al.  WNT signaling inducing activity in ascites predicts poor outcome in ovarian cancer , 2020, Theranostics.

[3]  J. Kos,et al.  Natural Killer Cells: Diverse Functions in Tumor Immunity and Defects in Pre-neoplastic and Neoplastic Stages of Tumorigenesis , 2019, Molecular therapy oncolytics.

[4]  W. Chung,et al.  Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers , 2019, British Journal of Cancer.

[5]  K. Beis,et al.  Learning the ABCs one at a time: structure and mechanism of ABC transporters. , 2019, Biochemical Society transactions.

[6]  H. Miyamoto,et al.  The Role of Androgen Receptor Signaling in Ovarian Cancer , 2019, Cells.

[7]  A. Lavie,et al.  Identifying small molecule probes of ENTPD5 through high throughput screening , 2018, bioRxiv.

[8]  É. Vivier,et al.  Natural killer cells and other innate lymphoid cells in cancer , 2018, Nature Reviews Immunology.

[9]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[10]  K. Nephew,et al.  Epigenetic Crosstalk between the Tumor Microenvironment and Ovarian Cancer Cells: A Therapeutic Road Less Traveled , 2018, Cancers.

[11]  G. Marone,et al.  Eosinophils: The unsung heroes in cancer? , 2018, Oncoimmunology.

[12]  Jingxin Ding,et al.  The positivity of estrogen receptor and progesterone receptor may not be associated with metastasis and recurrence in epithelial ovarian cancer , 2017, Scientific Reports.

[13]  M. Falasca,et al.  ABC Transporters in Cancer Stem Cells: Beyond Chemoresistance , 2017, International journal of molecular sciences.

[14]  A. Avan,et al.  Clinical Significance and Prognosis Value of Wnt Signaling Pathway in Cervical Cancer , 2017, Journal of cellular biochemistry.

[15]  L. Kiemeney,et al.  History of hypertension, heart disease, and diabetes and ovarian cancer patient survival: evidence from the ovarian cancer association consortium , 2017, Cancer Causes & Control.

[16]  Oleg Timofeev,et al.  Mutant p53 promotes tumor progression and metastasis by the endoplasmic reticulum UDPase ENTPD5 , 2016, Proceedings of the National Academy of Sciences.

[17]  Yue Yang,et al.  ENTPD5 Induces Apoptosis in Lung Cancer Cells via Regulating Caspase 3 Expression , 2015, PloS one.

[18]  F. Muggia,et al.  Targeting HER2 in ovarian and uterine cancers: challenges and future directions. , 2014, Gynecologic oncology.

[19]  V. Notario,et al.  The ENTPD5/mt-PCPH oncoprotein is a catalytically inactive member of the ectonucleoside triphosphate diphosphohydrolase family , 2013, International journal of oncology.

[20]  D. Sabatini,et al.  Pten-null tumors cohabiting the same lung display differential AKT activation and sensitivity to dietary restriction. , 2013, Cancer discovery.

[21]  Sudhir Srivastava,et al.  A Framework for Evaluating Biomarkers for Early Detection: Validation of Biomarker Panels for Ovarian Cancer , 2011, Cancer Prevention Research.

[22]  Sudhir Srivastava,et al.  Ovarian Cancer Biomarker Performance in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Specimens , 2011, Cancer Prevention Research.

[23]  Tak W. Mak,et al.  The ER UDPase ENTPD5 Promotes Protein N-Glycosylation, the Warburg Effect, and Proliferation in the PTEN Pathway , 2010, Cell.

[24]  V. Notario,et al.  PCPH/ENTPD5 expression confers to prostate cancer cells resistance against cisplatin-induced apoptosis through protein kinase Calpha-mediated Bcl-2 stabilization. , 2009, Cancer research.

[25]  V. Notario,et al.  PCPH/ENTPD5 expression enhances the invasiveness of human prostate cancer cells by a protein kinase C delta-dependent mechanism. , 2007, Cancer research.