肝癌患者术后肝外转移相关DNA拷贝数变异分子标志初探  

A preliminary study on molecular markers of DNA copy number aberration for extrahepatic metastasis in patients with hepatocellular carcinoma after surgery

作　　者：万小希 朱忠政[1] 闻炳基[1] 陈律[3] 鲍玲玲[1] 贺松琴[2] 胡柳燕[2] 丛文铭[4] 

机构地区：[1]安徽医科大学解放军113临床学院肿瘤科,宁波315040 [2]中国人民解放军第一一三医院肿瘤科 [3]宁波大学医学院 [4]第二军医大学东方肝胆外科医院病理科

出　　处：《中华肝胆外科杂志》2016年第8期522-525,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：南京军区医学科技创新基金（14ZD07,08MA023）;宁波市自然科学基金（2009A610126）

摘　　要：目的探讨肝细胞癌（HCC）患者术后肝外转移相关DNA拷贝数变异（CNA）的分子标志。方法采用微阵列比较基因组杂交技术检测66例HCC患者的全基因组CNAs。通过Cox生存模型分析CNAs与HCC术后肝外转移的相关性。结果单因素分析显示，6p21．32增益、15q11．2增益、20q12-13．13增益、4q12丢失和4q28．1—35．2丢失等5个CNAs与肝外转移风险显著相关（均P〈0．05）。多元逐步Cox回归分析显示，6p21．32增益（HR=3．65，95％CI=1．38～9．62）、4q28．1-35．2丢失（HR=0．24，95％CI=0．09～0．65）以及高血压病史和TNM分期是肝外转移风险的独立影响因素。6p21．32增益、6p21．32无增益／4q28．1—35．2丢失以及6p21．32无增益／4q28．1—35．2无丢失3组HCC患者的无转移生存期差异有统计学意义（P〈0．05）。结论6p21．32增益和4q28．1—35．2丢失是HCC患者术后肝外转移的独立预后因素，可用于肝外转移的风险预判。Objective To investigate the molecular markers of DNA copy number aberrations （CNAs） for extrahepatie metastasis in postoperative hepatocellular carcinoma （ HCC ）. Methods The genomic CNA of 66 HCC samples was detected by high-resolution Agilent 244K array comparative genomic hybridization. The correlation between CNAs and extrahepatic metastasis in postoperative HCC was analyzed using univariate and multiple stepwise Cox regression models. Results Univariate analysis showed that gains at 6p21.32, 15q11. 2 and 20q12-13.13, and losses at 4q12 and 4q28.1-35.2, together with a history of hypertension, complete tumor capsule, TNM stage, platelet count and prothrombin time, were associated with increased risk of extrabepatic metastasis （ all P 〈 0.05 ）. Multiple stcpwise Cox regression analyses revealed that 6p21.32 gain （FIR = 3.65, 95% CI = 1.38 - 9.62） and 4q28.1-35.2 loss （ HR = 0. 24, 95% CI = 0. 09 - 0.65 ） , together with a history of hypertension and TNM stage, were independent prognostic markers of extrahepatic metastasis. Survival analysis showed that non-metastatic survival among the 3 groups of HCCs with 6p21.32 gain, with 4q28.1-35.2 loss but without 6p21.32 gain, and without 6p21.32 gain and with 4q28.1-35.2 loss were significantly different （ log-rank test, P 〈 0.05 ）. Conclusion Both 6p21.32 gain and 4q28.1-35.2 loss in HCC were two independent prognostic markers of postoperative extrahepatic metastasis. These findings may help to identify patients who are at risk of extrahepatic metastasis after surgery.

关 键 词：肝细胞癌 肝外转移 微阵列比较基因组杂交 拷贝数变异 

分 类 号：R735.7[医药卫生—肿瘤]