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  

Expression of ZNF692 gene in clear cell renal cell carcinoma and its relationship with prognosis

作　　者：徐兆平[1] 王浩飞[1] XU Zhaoping;WANG Haofei(Department of Urology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院泌尿外科,上海200025

出　　处：《诊断学理论与实践》2020年第3期292-296,共5页Journal of Diagnostics Concepts & Practice

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-P ZNF692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<0.0001)及无事件生存期(Logrank统计分析,P<0.0001)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。Objective:To analyze the expression and prognostic value of ZNF692 gene 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 of ZNF692 expression 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 determine ZNF692 gene expression.Upstream regulation mechanism of ZNF692 gene 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 with ZNF692 gene knockdown were detected and the function of ZNF692 gene was analyzed.Results:TCGA data extraction and analysis of the clinical samples revealed that ZNF692 gene was highly expressed in ccRCC cancer tissue compared with paracancerous tissue,and the high level of ZNF692 gene expression predicted a poor prognosis.Patients with high ZNF692 gene expression had shorter overall survival and event-free survival than those with low ZNF692 gene expression.High expression of ZNF692 gene was correlated with activation of c-MYC transcription.In regulatory region of ZNF692 gene,H3 K27 ac was enriched and in a highly activated transcription state.Knockdown of ZNF692 gene inhibited cell proliferation in ccRCC.Conclusions:ZNF692 as a potential oncogene is involved in the development and progress of ccRCC,and high expression of ZNF692 in ccRCC predicts a poor prognosis.

关 键 词：肾透明细胞癌 ZNF692基因 预后 机制 

分 类 号：R737.11[医药卫生—肿瘤]