染色体8q拷贝数变异与肝细胞癌患者术后总生存期的相关性及其靶基因筛选  

Association of Chromosome 8q Copy Number Aberration with Postoperative Overall Survival of Patients with Hepatocellular Carcinoma and Screening of Potential Target Genes

作　　者：赵昆[1] 徐菊英 许青[1,3] 朱忠政 ZHAO Kun1,XU Ju-ying2,XU Qing1,3,ZHUZhong-zheng3(1.Shanghai Clinical College of Anhui Medical University,Shanghai 200072,China;2.Department of Medical Affairs,No.113 Hospital of People＇s Liberation Army,Ningbo 315040,China3.Department of Oncology,Shanghai Tenth People＇s Hospital,Shanghai 200072,Chin)

机构地区：[1]安徽医科大学上海临床学院,上海市200072 [2]中国人民解放军第一一三医院医务处,浙江省宁波市315040 [3]上海市第十人民医院肿瘤科,上海市200072

出　　处：《中国全科医学》2018年第18期2190-2195,共6页Chinese General Practice

基　　金：南京军区医学科技创新课题(14ZD07;08MA023);宁波市自然科学基金资助项目(2009A610126);宁波市C50-社会发展科技攻关项目(2014C50072)

摘　　要：目的探讨染色体8q拷贝数变异(CNA)与肝细胞癌(HCC)患者术后总生存期(OS)的关系,并筛选生存相关CNA内的潜在靶基因。方法收集2007—2008年于第二军医大学附属东方肝胆外科医院手术住院的HCC患者187例为研究对象。收集患者一般资料,检测其染色体8q CNA、染色体8q24.13-24.3片段内50个已知基因mRNA表达水平;术后对患者进行随访,最终共66例患者完成随访。一般资料、染色体8q内各高频CNA(增益发生率>20%)片段与OS的相关性分析采用Log-rank检验;采用Cox比例风险回归模型分析OS的影响因素;生存曲线比较采用Log-rank检验;染色体8q24.13-24.3增益HCC患者和8q24.13-24.3无增益HCC患者基因mRNA表达水平比较采用Mann-Whitney U检验。结果 HCC患者糖尿病史、有无完整肿瘤包膜、TNM分期与OS有相关性(P<0.05)。单因素Cox比例风险回归模型分析结果显示,染色体8q24.13-24.3增益与OS有相关性(P<0.05);多因素Cox比例风险回归模型分析结果显示,染色体8q24.13-24.3增益、有无糖尿病史、有无完整肿瘤包膜、TNM分期是OS的影响因素(P<0.05)。生存分析结果显示,染色体8q24.13-24.3增益HCC患者生存率低于染色体8q24.13-24.3无增益HCC患者(P<0.05)。染色体8q24.13-24.3增益HCC患者C8orf76、ATAD2、WDYHV1、FBXO32、TMEM65、TATDN1、ZNF572、SQLE、KIAA0196、NSMCE2、PVT1、FAM49B、ASAP1、NDRG1、ZFAT、KHDRBS3、EIF2C2 mRNA表达水平高于染色体8q24.13-24.3无增益HCC患者(P<0.000 1)。结论染色体8q24.13-24.3增益与HCC患者OS有关,可作为HCC的一个预后预测因子。ATAD2、PVT1、NDRG1拷贝数依赖性表达上调可能参与了HCC不良预后的演进过程。Objective To investigate the association of chromosome arm 8q copy number aberration（CNA） with postoperative overall survival（OS） of patients with hepatocellular carcinoma（HCC）,and to screen for potential target genes in the survival-related CNA（s）.Methods A total of 187 HCC patients who received operation in Eastern Hepatobiliary Surgery Hospital,Second Military Medical University from 2007 to 2008 and postoperative follow-up（66 completed the followup） were enrolled in the study.We collected their clinicopathological data as well as follow-up data,including the mRNA expression levels of 50 known genes in chromosome 8q24.13-24.3 segment.The associations of the clinicopathological factors and high-frequency CNA（s）（20%） in chromosome arm 8q with OS were analyzed using the Log-rank test.The confounding factors for OS were analyzed using the Cox proportional hazards model.The survival curves were analyzed using the Kaplan-Meier method.The expression levels between the HCC patients with 8q24.13-24.3 gain and those without were compared by the MannWhitney U test.Results Diabetes history,absence of complete tumoral capsule and advanced TNM stage were associated with OS（P〈0.05）.Univariate Cox analysis showed that chromosome 8q24.13-24.3 gain was associated with OS（P〈0.05）.Multivariate Cox analysis showed that 8q24.13-24.3 gain,diabetes history,absence of complete tumoral capsule and advanced TNM stage were prognostic factors for OS（P〈0.05）.Survival analysis showed that the survival rate of the patients with 8q24.13-24.3 gain was lower than that of those without（P〈0.05）.The mRNA expression levels of 17 genes in 8q24.13-24.3 including C8 orf76,ATAD2,WDYHV1,FBXO32,TMEM65,TATDN1,ZNF572,SQLE,KIAA0196,NSMCE2,PVT1,FAM49 B,ASAP1,NDRG1,ZFAT,KHDRBS3 and EIF2C2 were significantly increased in patients with 8q24.13-24.3 gain compared to those without（P〈0.000 1）.Conclusion Copy number gain at 8q24.13-24.3 is a potential prognostic marker for reduced OS for HCC patients,and DNA

关 键 词：癌 肝细胞 预后 DNA拷贝数变异 基因表达 

分 类 号：R730.261[医药卫生—肿瘤]