DNA拷贝数变异与HBV相关肝细胞癌术后肝内复发的相关性研究

Genomic analyses of DNA copy number alterations with intrahepatic recurrence in HBV-associated hepatocellular carcinoma after hepatectomy

目的探讨利用DNA拷贝数变异(CNA)预测HBV相关肝细胞癌(HCC)术后肝内复发的可行性。方法采用高分辨率微阵列比较基因组杂交技术(aCGH),对47例HBV相关HCC肿瘤细胞基因组DNA的CNA情况进行检测;通过Kaplan-Meier生存分析和Cox风险比例模型,评估CNAs对HCC术后复发的影响。结果单因素生存分析结果显示,16q11.2-22.1是否丢失对HCC术后复发有显著影响(P=0.001),而基因组内其他CNAs均与复发无关。与16q11.2-22.1未丢失者相比,16q11.2-22.1丢失HCC患者的术后复发危险比(HR)为4.59(95%CI=1.64～12.84,P=0.004)。多因素Cox回归分析显示,16q11.2-22.1是否丢失是HCC术后复发的独立预测因素(HR=4.64,95%CI=1.65～13.06,P=0.004)。结论染色体片段16q11.2-22.1是否丢失是预测HBV相关HCC术后肝内复发的有效指标。

Objective To investigate the prognostic value of DNA copy number alterations （CNAs） in predicting intrahepatic recurrence of HBV-associated hepatocellular carcinoma after hepatectomy. Methods The genomie CNA status in tumor tissue DNA was detected by high-resolution array comparative genomic hybridization （aCGH） in 47 HBV-associated HCC samples. The follow-up time of these patients was 3. 1-28. 0 months. The CNAs were analyzed for their association with intrahepatic recurrence by Kaplan- Meier and Cox proportional hazards models. Results Univariate analysis of the association between CNAs and intrahepatic recurrence revealed that 16ql 1.2-22. 1 loss was significantly associated with recurrence （ P = 0. 001 ）. HCC cases with 16ql 1.2-22. 1 loss as com- pared to those without the loss had a 4. 59-fold （95% CI = 1.64-12. 84 ,P = O. 004 ） increased hazard ratio （HR） for recurrence. Mult- ivariate analyses including 16ql 1.2-22. 1 loss and tumor stage showed that 16ql 1.2-22. 1 loss was an independent predictive factor for recurrence （HR =4. 64,95% CI = 1.65-13.06,P = 0. 004）. Conclusion These findings suggest that 16q11.2-22. 1 loss is associat- ed with intrahepatic recurrence of HBV-associated hepatocellular carcinoma after hepatectomy and may be used as a predictive marker.