乙型肝炎病毒相关性肝细胞癌中分泌型卷曲相关蛋白基因甲基化分析

目的 研究HBV相关性肝细胞癌(HCC)中分泌型卷曲相关蛋白(SFRP)1、SFRP2基冈甲基化状态及其与肝细胞癌发牛发展的关系.方法 利用甲基化特异性聚合酶链反应(MSP)法检测45例肝细胞癌患者术中取得癌组织、癌旁组织及6例胆囊结石或肝脏血管瘤患者正常肝组织中SFRP1、SFRP2基因的甲基化状态.数据行X2检验、Fisher's 确切概率法统计分析.结果 在45例HCC患者中,癌组织和癌旁组织中SFRP1基因的甲基化率分别占62.2%和35.6%(X2=6.403,P＜0.05);SFRP2基因的甲基化率分别占51.1%和28.9%(X2=4.630,P＜0.05);6例正常肝组织均未检测到甲基化.癌组织中SFRPI与SFRP2基因甲基化在性别、年龄、HBV血清标志物、癌旁组织类型、有无转移和病理分级等因素之间差异均无统计学意义(P＞0.05),癌组织中SFRP1与SFRP2基因异常甲基化具有线性相关性(r=0.381,P=0.01).结论 SFRP1和SFRP2基因甲基化在HBV相关性HCC中是个频发事件,将来有可能作为一种预测HCC形成的分子生物学标志物.

Analysis of the methylation status of secreted frizzled-related protein genes in hepatitis B virus-related hepatocellular carcinoma

Objective To study the methylation status of secreted frizzled-related protein (SFRP) 1 and SFRP2 genes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and the relationship between the methylation status of the two genes and the development of HCC.Methods Using methylation-specific polymerase chain reaction (MSP) to detect methylation status of SFRP1 and SFRP2 genes of 45 specimens of HCC tissue and adjacent non-tumorous liver tissue from HCC patients during operations,and 6 normal liver tissues from patients with cholecystolithiasis or hepatic hemangiomas. The data were analyzed by chi-square test and Fisher exact test. Results SFRP1 gene methylation was detected in 28 HCC tissues and 16 adjacent non-tumorous liver tissues,accounted for 62.2% and 35.6%,respectively;and SFRP2 gene methylation was detected in 23 HCC tissues and 13 adjacent non-tumorous liver tissues,accounted for 51.1% and 28.9%,respectively;while no methylation was detected in 6 samples of normal liver tissues. There was no significant difference between the methylation of SFRP1 and SFRP2 genes in HCC tissues and gender,age,HBV serum markers,types of adjacent non-tumorous liver tissues,metastasis and pathological stage (P＞0.05).The abnormal methylation status between SFRP1 and SFRP2 genes was linear correlated in HCC tissues (r=0.381,P=0.01).Conclusion Hypermethylation of SFRP1 and SFRP2 genes frequently occurs in HBV-related HCC,which may be an important molecular biomarker for prediction of hepatocarcinogenesis in the future.