诊断学理论与实践

诊断学理论与实践››2020,Vol. 19››Issue (03): 292-296.doi:10.16150/j.1671-2870.2020.03.016

• 论著 •上一篇下一篇

ZNF692基因在肾透明细胞癌中的表达及其与患者预后间关系的研究

徐兆平, 王浩飞()

  1. 开云网页登录 医学院附属瑞金医院泌尿外科,上海 200025
  • 收稿日期:2019-12-17出版日期:2020-06-25发布日期:2020-06-25
  • 通讯作者:王浩飞 E-mail:whf10728@rjh.com.cn

Expression ofZNF692gene in clear cell renal cell carcinoma and its relationship with prognosis

XU Zhaoping, WANG Haofei()

  1. Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Received:2019-12-17Online:2020-06-25Published:2020-06-25
  • Contact:WANG Haofei E-mail:whf10728@rjh.com.cn

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摘要：

目的：研究ZNF692基因在肾透明细胞癌（clear cell renal cell carcinoma, ccRCC）中的表达特征及其与患者预后间的关系,并分析ZNF692基因相关的调控机制。方法：采用癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库进行生物信息数据挖掘,提取516例ccRCC样本,分析ZNF692的表达特征及水平与ccRCC预后之间的关联,进一步分析ZNF692表达水平与DNA拷贝数、甲基化及组蛋白修饰间的关联,探索ZNF692的上游调控机制。收集本院20例ccRCC患者资料,采用实时定量反转录聚合酶链反应（quantitative reverse transcription polymerase chain reaction, qRT-PCR）检测癌及配对癌旁组织中ZNF692基因的表达水平,分析ZNF692表达与ccRCC患者预后间的关系;敲低ccRCC细胞株786-O 和769-PZNF692基因后,观察细胞的增殖状态,分析ZNF692的功能。结果：数据挖掘及临床样本分析提示,相对于癌旁组织,ZNF692在肿瘤组织中高表达（P<0.05）;ZNF692高表达的ccRCC患者总体生存期（Logrank统计分析,P<0.000 1）及无事件生存期（Logrank统计分析,P<0.000 1）低于低表达患者。数据库数据挖掘及临床样本分析提示ZNF692高表达与c-MYC转录激活相关;ZNF692转录调控处于高度转录活化的状态,组蛋白H3赖氨酸27位点乙酰化（H3K27ac）富集;敲低细胞株ZNF692基因后, ccRCC细胞增殖被显著抑制（P<0.05）。结论：ZNF692作为潜在癌基因参与了ccRCC的发生、发展,且其在ccRCC中高表达与患者预后不良相关。

关键词:肾透明细胞癌,ZNF692基因,预后,机制

Abstract:

Objective:To analyze the expression and prognostic value ofZNF692gene in clear cell renal cell carcinoma (ccRCC) and to explore the related regulation mechanism.Methods:The RNA-Seq and clinical data were extracted from The Cancer Genome Atlas (TCGA) database and the correlation ofZNF692expression with prognosis in the 516 ccRCC patients obtained were assessed. Twenty paired cancerous and paracancerous tissue samples of ccRCC patients were collected at Ruijin Hospital, and quantitative RT-PCR was used to determineZNF692gene expression. Upstream regulation mechanism ofZNF692gene was explored by analyzing gene expression level with DNA copy number, DNA methylation and histone modification. Cell proliferations in ccRCC cell lines 786-O and 769-P withZNF692gene knockdown were detected and the function ofZNF692gene was analyzed.Results:TCGA data extraction and analysis of the clinical samples revealed thatZNF692gene was highly expressed in ccRCC cancer tissue compared with paracancerous tissue, and the high level ofZNF692gene expression predicted a poor prognosis. Patients with highZNF692gene expression had shorter overall survival and event-free survival than those with lowZNF692gene expression. High expression ofZNF692gene was correlated with activation ofc-MYCtranscription. In regulatory region ofZNF692gene, H3K27ac was enriched and in a highly activated transcription state. Knockdown ofZNF692gene inhibited cell proliferation in ccRCC.Conclusions:ZNF692as a potential oncogene is involved in the development and progress of ccRCC, and high expression ofZNF692in ccRCC predicts a poor prognosis

Key words:Clear cell renal cell carcinoma,ZNF692gene,Prognosis,Mechanism

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