染色体8p拷贝数变异与肝细胞癌术后总生存的关系及靶基因筛选  

Association of chromosome 8p copy number alteration with postoperative survival of patients with hepatocellular carcinoma and screening of potential target genes

作　　者：王美玲[1] 姜斌[1] 丛文铭[2] 胡晓华[1] 董辉[2] 朱忠政[3] 

机构地区：[1]上海交通大学医学院附属第三人民医院肿瘤科,上海201900 [2]第二军医大学东方肝胆外科医院病理科 [3]解放军第113医院肿瘤科宁波市肿瘤风险与干预重点实验室

出　　处：《中华肝胆外科杂志》2015年第5期292-296,共5页Chinese Journal of Hepatobiliary Surgery

基　　金：国家自然科学基金（30470791）;南京军区医学科技创新基金（08MA023）;宁波市自然科学基金（2009A610126）

摘　　要：目的 探讨染色体8p拷贝数变异（CNA）与肝细胞癌（HCC）术后生存的关系,筛选生存相关CNA内的潜在靶基因.方法 纳入HCC手术患者187例,其中66例有完整术后生存随访资料.分别采用Agilent 244K微阵列比较基因组杂交和Affymetrix U133 Plus2.0基因芯片方法检测8p CNA和基因表达差异.结果 8p12丢失（31/66,47％）是HCC术后生存的独立预后因素.8p12丢失患者的死亡风险为无丢失患者的4.1倍（95％CI=1.8～9.4,P＜0.05）.8p12片段内基因丢失与mRNA表达的联合分析显示,基因丢失HCC组TMEM66、DCTN6和MAK16 3个基因的mRNA表达水平显著低于基因无丢失HCC组（均P＜0.05）和癌旁肝组（均P＜0.05）.结论 染色体8p12丢失是HCC患者术后生存不良的独立预后因素.TMEM66、DCTN6和MAK16基因拷贝数依赖性表达下调可能参与了HCC不良预后的演进过程.Objective To investigate the association of chromosome 8p copy number alteration （CNA） with postoperative survival of patients with hepatocellular carcinoma （HCC）,and to screen for possible target genes in the survival-related CNA （s） in 8p.Methods 187 HCC patients were enrolled into the study,which included 66 patients whose follow-up data were available and the follow-up was 2.6 ～ 73.3 months.High-resolution Agilent 244K comparative genomic hybridization （CGH） and Affymetrix U133 Plus2.0 expression arrays were used to screen for CNAs and gene expression differences in 8p.The associations between CNAs in 8p and survival were analyzed using the log-rank test,Kaplan-Meier survival analysis and Cox proportional hazards models.The gene expression levels between the groups were compared by the Mann-Whitney U test.Results Copy number loss on 8p12 （31/66,47%） was significantly associated with reduced survival rate,and HCC patients with 8p12 loss had a 4.1-fold （95% CI =1.8 ～ 9.4,P 〈 0.05） increased hazard ratio （HR） for death from HCC,as compared to those without the loss.The mRNA expression levels of the 3 genes in 8p12,including TMEM66,DCTN6,and MAK16,were significantly decreased in HCCs with gene loss than in HCCs without the loss （all P 〈 0.05）,and in non-tumorous liver tissues （all P 〈 0.05）.Conclusion Loss of 8p12 is an independent prognostic marker of unfavorable survival for patients with HCC,and underexpression of genes TMEM66,DCTN6,and MAK16,owing to 8p12 loss,contributed to unfavorable prognosis.

关 键 词：肝细胞癌 预后 分子标志 拷贝数变异 基因表达 

分 类 号：R737.902[医药卫生—肿瘤]