卵巢癌中ETV4基因高表达对患者预后的临床意义

doi:10.13418/j.issn.1001-165x.2019.02.021

中国临床解剖学杂志 ›› 2019, Vol. 37 ›› Issue (2): 217-222.doi: 10.13418/j.issn.1001-165x.2019.02.021

卵巢癌中ETV4基因高表达对患者预后的临床意义

俞鹏^1,2，　杨月³，　陆进^1,2，　赖桂华^1,2，　张浩轩^1,2

1. 组织移植安徽省重点实验室，安徽蚌埠 233030； 2. 蚌埠医学院人体解剖学教研室，安徽蚌埠 233000
3. 蚌埠医学院第一附属医院妇产科，安徽蚌埠 233000

收稿日期:2018-12-05 出版日期:2019-03-25 发布日期:2019-04-29
通讯作者: 张浩轩，硕士，副教授，E-mail:zhanghaoxuan@bbmc.edu.cn
作者简介:俞鹏（1979-），男,安徽芜湖人，实验师，主要从事基础医学研究，Tel：13955202521，E-mail:1619246807@qq.com
基金资助:
安徽省教育厅高校自然科学重点研究项目（KJ2018A0236）；蚌埠医学院自然科学基金面上项目（BYKY1758）

The correlation of the high expression of ETV4 gene with prognosis of patients with ovarian cancer

YU Peng ^1,2, YANG Yue ³, LU Jin ^1,2, LAI Gui-hua ^1,2, ZHANG Hao-xuan ^1,2

1.Anhui Key Laboratory of Tissue Transplantation, Bengbu 233000, Anhui Province; 2. Department of Human Anatomy, Bengbu Medical College, Bengbu 233030; 3.Department of Obstetrics and Gynecology, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China

Received:2018-12-05 Online:2019-03-25 Published:2019-04-29

摘要/Abstract

摘要：

目的　探讨ETV4在卵巢癌中的表达及与预后的关系。方法　分别利用BioGPS数据库、Oncomine数据库、癌症细胞系百科全书（CCLE）和Kaplan-Meier Plotter数据库分析ETV4基因在正常人体组织中的表达、卵巢癌组织中的表达，以及卵巢癌患者预后生存分析；利用cBioPortal数据库分析ETV4在卵巢癌中基因突变和预后关系。结果　BioGPS数据库分析结果显示ETV4在正常卵巢组织低表达；Oncomine数据库检索出340项，ETV4表达水平有差异意义的结果32项，其中ETV4表达增高30项，ETV4表达降低2项；对符合设定条件的2项研究进行Meta分析发现，ETV4在卵巢癌组织中呈高表达状态（P<0.05）；CCLE分析结果显示ETV4在卵巢癌细胞中高表达；Kaplan-Meier Plotter数据库结果显示，ETV4高表达组的卵巢癌患者总体生存时间（OS）与无病生存时间（DFS）较低表达组均显著延长（P<0.05）。cBioPortal数据库结果显示ETV4在卵巢癌中基因突变率为2.5%，但对卵巢癌患者的OS与DFS均无显著影响（P>0.05）。结论　ETV4在卵巢癌组织中高表达，且具有显著延长卵巢癌患者OS与DFS的作用，可作为卵巢癌临床预后的候选标志物；ETV4基因的突变对卵巢癌患者的OS与DFS无显著影响。

关键词: , 卵巢癌, 　基因, 　肿瘤, 　生存

Abstract:

Objective　To investigate the correlation of the high expression of ETS Translocation Variant(ETV4) gene with prognosis of patients with ovarian cancer. Methods　The expression levels of ETV4 gene in normal human tissue and ovarian cancer tissue, and patients survival were analyzed using the BioGPS database, Oncomine database, Encyclopedia(CCLE) and Kaplan-Meier Plotter database. The relationship between the gene mutation of ETV4 in ovarian cancer and prognosis of patients was analyzed using the cBioPortal database.　Results The analysis results of BioGPS database showed that the expression of ETV4 gene was low in normal ovarian tissue. Among 340 items searched from Oncomine database, 32 items showed that the expression levels of ETV4 increased, and 2 items showed that the expression levels of ETV4 decreased. Meta-analysis of two studies showed that the ETV4 gene was highly expressed in ovarian cancer tissues (P<0.05). CCLE analysis showed that the ETV4 gene was highly expressed in ovarian cancer cells. Kaplan-Meier Plotter database showed that the Overall Survival (OS) and Disease Free Survival (DFS) in ovarian cancer patients with high expression levels of ETV4 gene were significantly prolonged compared with ovarian cancer patients with low expression levels of ETV4 gene (P<0.05). The results of the cBioPortal database showed that the gene mutation rate of ETV4 in ovarian cancer was 2.5%, which had no significant effect on OS and DFS in patients with ovarian cancer (P>0.05).　Conclusions　The ETV4 gene is highly expressed in ovarian cancer tissue, which has a significant prolongation of OS and DFS in patients with ovarian cancer, and can be used as a candidate for assessment of clinical prognosis of patients ovarian cancer. The mutation of ETV4 gene has no significant effects on the OS and DFS of ovarian cancer patients.

Key words: Ovarian Cancer, 　Gene, 　Tumor, 　Survival

俞鹏,杨月,陆进,赖桂华,张浩轩. 卵巢癌中ETV4基因高表达对患者预后的临床意义[J]. 中国临床解剖学杂志, 2019, 37(2): 217-222.

YU Peng, YANG Yue, LU Jin,LAI Gui-hua, ZHANG Hao-xuan. The correlation of the high expression of ETV4 gene with prognosis of patients with ovarian cancer[J]. Chinese Journal Of Clinical Anatomy, 2019, 37(2): 217-222.

参考文献 24

[1]	陆进, 杨月, 闫坤, 等. 基于多种基因数据库分析乳清酸性蛋白4-二硫键核心结构域2(WFDC2)在卵巢癌中表达及意义[J]. 细胞与分子免疫学杂志, 2018, 34(6): 528-534.
[2]	Brightwell R, Eng K, Eele S. Use of hematologic biomarkers during chemotherapy predicts survival in ovarian cancer patients[J]. Eur J Gynaecol Oncol, 2017, 38(3): 378-381.
[3]	Sans M, Gharpure K, Tibshirani R, et al. Metabolic markers and statistical prediction of serous ovarian cancer aggressiveness by ambient ionization mass spectrometry imaging[J]. Cancer Res, 2017, 77(11): 2903-2913.
[4]	Lu X, Lu J, Liao B, et al. Driver pattern identification over the gene co-expression of drug response in ovarian cancer by integrating high throughput genomics data[J/OL]. Sci Rep, 2017, 7(1): 16188.
[5]	Oh S, Shin S, Janknecht R. ETV1, 4 and 5: an oncogenic subfamily of ETS transcription factors[J]. Biochim Biophys Acta, 2012, 1826(1): 1-12.
[6]	Bièche I, Tozlu S, Girault I, et al. Expression of PEA3/E1AF/ETV4, an Ets-related transcription factor, in breast tumors: positive links to MMP2, NRG1 and CGB expression[J]. Carcinogenesis, 2004, 25(3): 405-411.
[7]	Qi M, Liu Z, Shen C, et al. Overexpression of ETV4 is associated with poor prognosis in prostate cancer: involvement of uPA/uPAR and MMPs[J]. Tumor Biol, 2015, 36(5): 3565-3572.
[8]	刘贵敏, 张丽军, 王红杰, 等. MMP-2、MMP-9在JAK2 V617F阳性的骨髓增殖性肿瘤中表达增强[J]. 细胞与分子免疫学杂志, 2017, 33(3): 372-375.
[9]	刘浩, 刘心, 王义涛, 等. 人ETV4蛋白截短体的构建与其在结直肠中的功能分析[J]. 重庆医科大学学报, 2018, 43(9): 1199-1204.
[10]	Yoshihara K, Tajima A, Komata D, et al. Gene expression profiling of advanced stage serous ovarian cancers distinguishes novel subclasses and implicates ZEB2 in tumor progression and prognosis[J]. Cancer Sci, 2009 , 100(8): 1421-1428.
[11]	Welsh JB, Zarrinkar PP, Sapinoso LM, et al. Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer[J]. Proc Natl Acad Sci U S A, 2001, 98(3): 1176-1181.
[12]	Choe SR, Kim YN, Park CG, et al. RCP induces FAK phosphorylation and ovarian cancer cell invasion with inhibition by curcumin[J/OL]. Exp Mol Med, 2018, 50(4): 52.
[13]	Redell MS, Tweardy DJ. Targeting transcription factors for cancer therapy[J]. Curr Pharm Des, 2005, 11(22): 2873-2887.
[14]	Yuan ZY, Dai T, Wang SS, et al. Overexpression of ETV4 protein in triple-negative breast cancer is associated with a higher risk of distant metastasis[J]. Onco Targets Ther, 2014, 7: 1733-1742.
[15]	薛成军, 文娟娟, 刘艺, 等. ETV4在乳腺癌中的表达及其与血管生成的关系[J]. 中国老年学杂志, 2014, 34(6): 1458-1461.
[16]	Spinella F, Rosanò L, Del Duca M, et al. Endothelin-1 inhibits proly1 hydroxylase domain 2 to activate hypoxia-inducible factor-1 alpha in melanoma cells[J]. PLoS One, 2010, 5(6): e11241.
[17]	Wollenick K, Hu J, Kristiansen G, et al. Synthetic transactivation screening reveals ETV4 as broad coactivator of hypoxia-inducible factor signaling[J]. Nucleic Acids Res, 2012, 40(5): 1928-1943.
[18]	Westermarck J, Kähäri VM. Regulation of matrix metalloproteinase expression in tumor invasion[J]. FASEB J, 1999, 13(8): 781-792.
[19]	Chen Y, Chen L, Li JY, et al. ERβ and PEA3 co-activate IL-8 expression and promote the invasion of breast cancer cells[J]. Cancer Biol Ther, 2011, 11(5): 497-511.
[20]	Hung YP, Fletcher CD, Hornick JL. Evaluation of ETV4 and WT1 expression in CIC-rearranged sarcomas and histologic mimics[J]. Mod Pathol, 2016, 29(11): 1324-1334.
[21]	Kim E, Kim D, Lee JS, et al. Capicua suppresses hepatocellular carcinoma progression by controlling ETV4-MMP1 axis[J]. Hepatology, 2018, 67(6): 2287-2301.
[22]	Sharrocks AD. The ETS-domain transcription factor family[J]. Nat Rev Mol Cell Biol, 2001, 2(11): 827-837．
[23]	Currie SL, Lau DKW, Doane JJ, et al. Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4 and ETV5[J]. Nucleic Acids Res, 2017, 45(5): 2223-2241.
[24]	Xiao J, Yang S, Shen P, et al. Phosphorylation of ETV4 at Ser73 by ERK kinase could block ETV4 ubiquitination degradation in colorectal cancer[J]. Biochem Biophys Res Commun, 2017, 486(4): 1062-1068.

卵巢癌中ETV4基因高表达对患者预后的临床意义

The correlation of the high expression of ETV4 gene with prognosis of patients with ovarian cancer

可视化

摘要/Abstract

引用本文

使用本文

参考文献 24

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	江剑宏, 段仁鹏, 李晓锋. 国人胆道三维重建解剖变异应用研究[J]. 中国临床解剖学杂志, 2024, 42(1): 1-4.
[2]	郭红志, 王瑜, 张加琪, 梁海彬, 马梓玮, 冯伟, 吴忧, 司子燚. 血管铸型结合CT三维模型评估先兆子痫胎盘血管结构[J]. 中国临床解剖学杂志, 2024, 42(1): 5-10.
[3]	李佳伟, 张静, 李灿然, 兰文杰, 籍庆余, 郭志勇, 张云凤, 刘启, 陈清威, 李筱贺. 蒙古族人群股骨近端解剖参数X线测量[J]. 中国临床解剖学杂志, 2024, 42(1): 11-16.
[4]	李琨, 张燕, 郭冉, 郝咪咪, 吴轩宇, 徐艺芳, 王超群, 马文童, 张灵淇, 杨宏宇, 李志军, 张少杰, 王星. 儿童及青少年枕颈角与后枕颈角数字化测量及其临床意义[J]. 中国临床解剖学杂志, 2024, 42(1): 17-20.
[5]	李文, 杨思艺, 黄蕾, 卿霁雯, 蒋松涛, 张磊. 基于MRI探讨Lisfranc韧带的形态学特点及临床意义[J]. 中国临床解剖学杂志, 2024, 42(1): 21-25.
[6]	李凡凡, 徐阳, 王晓旭. 紫草素调节Nrf2/HO-1信号通路对实验性大鼠肉芽肿性小叶性乳腺炎的治疗作用研究[J]. 中国临床解剖学杂志, 2024, 42(1): 26-32.
[7]	王兴航, 丁佳媛, 李放, 包翠芬, 阎丽菁. 人参皂苷Rg1通过抑制NLRP3炎症小体途径减轻氧糖剥夺/复供后小胶质细胞炎症反应[J]. 中国临床解剖学杂志, 2024, 42(1): 33-41.
[8]	程莹莹, 武建军, 蔡海燕, 焦旭文, 马江波, 丁银秀. 体外炎性诱导星形胶质细胞激活及功能分析[J]. 中国临床解剖学杂志, 2024, 42(1): 42-46.
[9]	祁志, 杨力, 贾秋叶, 陈浩伦, 段兆达, 吴春云. 依达拉奉经MAPKs通路对脂多糖激活的小胶质细胞Sirt3表达调控[J]. 中国临床解剖学杂志, 2024, 42(1): 47-53.
[10]	张晶晶, 王洪新. 黄芩苷通过PDGF/P38 MAPK信号通路对肺动脉高压大鼠的保护作用[J]. 中国临床解剖学杂志, 2024, 42(1): 54-58.
[11]	乐钦, 陈荣丽, 熊婧熙, 王婷怡, 蔡志恒, 易秋实, 曾心怡. 白芨多糖对大鼠跨区皮瓣choke区的影响[J]. 中国临床解剖学杂志, 2024, 42(1): 59-64.
[12]	李笑予, 张磊, 付磊, 李东波, 汪国友. 三步接骨法治疗Sanders Ⅱ型跟骨骨折的有限元研究[J]. 中国临床解剖学杂志, 2024, 42(1): 65-70.
[13]	吴研飞, 马剑雄, 卢斌, 王颖, 柏豪豪, 靳洪震, 马信龙. CT后处理技术重建CT值与终板抗压强度的相关性研究[J]. 中国临床解剖学杂志, 2024, 42(1): 71-76.
[14]	庄万强, 唐毅, 骆勇刚, 张辉. 关节镜联合胫骨高位截骨术对髌骨位置及髌股关节功能影响的早中期回顾性研究[J]. 中国临床解剖学杂志, 2024, 42(1): 77-82.
[15]	罗鹰, 窦伟誉, 吴小杭, 陈璟昆, 彭昌贵, 潘剑英 . 微创海马钢板内固定治疗跟骨骨折并发症的影响因素[J]. 中国临床解剖学杂志, 2024, 42(1): 83-88.