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目的:探讨HBV感染和CDKN2A异常甲基化之间的潜在关联及其相互作用在肝癌形成过程中的作用。方法:对44例肝癌患者癌组织及癌旁组织CDKN2A甲基化状况、血清HBV感染标志物等到进行了检测分析。血清HBV、HCV感染标志物采用全自动化学发光分析仪进行检测。采用酚、氯仿法抽提组织DNA,用CDKN2A甲基化特异性引物进行PCR扩增,并检测特异性产物。患者按HBV感染情况进行分组,统计分析。结果:CDKN2A甲基化产物在肝癌组织中的总检出率为70.5%(31/44)。其中,HBV相关肝癌组和非病毒相关肝癌组CDKN2A甲基化率为90.6%(29/32)和16.7%(2/12),P=0.000。对HBV相关肝癌进一步分组分析,HBsAg+/HBeAg+、HBsAg+/HBeAg-及HBcAb+/HBcAb-三组,三组之间差异无统计学意义(P=0.568)。经非参数相关和logistic回归分析,发现:CDKN2A甲基化与性别、肿瘤分化程度无明显相关(R2=0.11,P=0.650),而与HBV感染,特别是HBsAg密切相关(R2=0.37,P=0.02)。结论:在肝癌形成过程中,HBV可能通过促进抑癌基因,如CDKN2A等的异常甲基化,使CDKN2A失活,肝细胞正常的生长调控机制失常,形成肝癌,这也可能是HBV导致肝癌形成的机制之一。
Objective: To investigate the potential relationship between HBV infection and aberrant methylation of CDKN2A and the role of its interaction in the formation of hepatocellular carcinoma. Methods: The methylation status of CDKN2A and the markers of serum HBV infection in 44 cases of HCC patients were detected. Serum HBV, HCV infection markers using automatic chemiluminescence analyzer for testing. Tissue DNA was extracted by phenol and chloroform method, PCR amplification was performed by CDKN2A methylation specific primers, and specific products were detected. Patients by HBV infection grouping, statistical analysis. Results: The overall detection rate of CDKN2A methylation in HCC tissues was 70.5% (31/44). Among them, the methylation rates of CDKN2A in HBV-related liver cancer group and non-virus-related liver cancer group were 90.6% (29/32) and 16.7% (2/12), respectively, P = 0.000. There was no significant difference between the three groups for further subgroup analysis of HBV-related HCC, HBsAg + / HBeAg +, HBsAg + / HBeAg- and HBcAb + / HBcAb- (P = 0.568). By non-parametric correlation and logistic regression analysis, it was found that there was no significant correlation between methylation of CDKN2A and sex and tumor differentiation (R2 = 0.11, P = 0.650), but closely related to HBV infection, especially HBsAg = 0.02). Conclusion: HBV may inactivate CDKN2A by up-regulating methylation of tumor suppressor genes such as CDKN2A during the process of hepatocarcinoma formation, resulting in the formation of hepatocellular carcinoma, which may also lead to the formation of hepatocellular carcinoma by HBV One of the mechanisms.