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目的探讨与肝细胞癌(HCC)远处转移相关的DNA拷贝数变异(copy number alteration,CNA)分子标志。方法采用高分辨率Agilent 244K微阵列比较基因组杂交(aCGH)方法检测63例HCC样本基因组DNA的CNA特征。以Log-rank检验、Kaplan-Meier生存分析以及Cox风险比例模型,分析各DNA片段CNA与HCC远处转移的相关性。结果染色体片段12p12.2-13.31丢失是HCC患者远处转移的显著危险因素(P<0.01,Log-rank检验)。与非丢失者相比,12p12.2-13.31丢失HCC患者的远处转移风险比(hazard ratio,HR)为22.98(95%CI=4.29～123.22,P<0.01)。多变量Cox回归分析显示,12p12.2-13.31丢失是HCC远处转移的独立预测因素(HR=7.94,95%CI=1.14～55.61,P<0.05)。结论染色体片段12p12.2-13.31丢失增加HCC远处转移风险,可作为预测HCC远处转移的一个分子标志。
Objective To investigate the molecular markers of DNA copy number alteration (CNA) associated with the distant metastasis of hepatocellular carcinoma (HCC). Methods High-resolution Agilent 244K microarray comparative genomic hybridization (aCGH) method was used to detect the CNA characteristics of genomic DNA from 63 HCC samples. Log-rank test, Kaplan-Meier survival analysis and Cox proportional hazard model were used to analyze the correlation between CNA and distant metastasis of HCC. Results Loss of chromosome 12p12.2-13.31 was a significant risk factor for distant metastasis in HCC patients (P <0.01, Log-rank test). The hazard ratio (HR) of distant metastasis was 12.92% (95% CI = 4.29 ~ 123.22, P <0.01) in patients with HCC with 12p12.2-13.31 loss compared with those without loss. Multivariate Cox regression analysis showed that loss of 12p12.2-13.31 was an independent predictor of distant metastasis of HCC (HR = 7.94, 95% CI = 1.14-55.61, P <0.05). Conclusion The loss of chromosome fragment 12p12.2-13.31 increases the risk of distant metastasis of HCC and may serve as a molecular marker for predicting the distant metastasis of HCC.