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目的 :检测抑癌基因带有血小板凝血酶敏感蛋白样模体的解联蛋白金属蛋白酶9(a disintegrin-like and metalloprotease with thromobospondin type 1 motif 9,ADAMTS 9)在肝癌组织中的甲基化情况,并探讨ADAMTS 9基因甲基化与肝癌发生、进展及预后的关系。方法 :收集132例肝细胞癌组织及对应的132例癌旁肝硬化组织,15例正常肝组织;采用甲基化特异性聚合酶链反应(methylation specii c polyerase chain reaction,MSP)检测ADAMTS 9基因的甲基化状态。结合患者临床病理资料及生存期,观察ADAMTS 9基因甲基化状态与肝细胞癌发生及判断预后的价值。结果 :在正常肝组织中未检测到ADAMTS9基因的甲基化状态,肝细胞癌组织中ADAMTS9基因的甲基化阳性率为66.67%,在癌旁肝硬化组织中ADAMTS9基因的甲基化阳性率为29.55%;统计分析结果显示,3组间甲基化阳性率有明显的差别(χ2=49.918,P=0.000)。结合临床病理资料,有门脉瘤栓患者的甲基化阳性率(78.72%)大于无门脉瘤栓患者的甲基化阳性率(60.00%),差异有统计学意义(P=0.029)。Ⅰ~Ⅱ期肿瘤患者的甲基化阳性率高于Ⅲ~Ⅳ期肿瘤患者,差异有统计学意义(P=0.008)。生存分析结果显示,ADAMTS9基因甲基化阳性患者的2年生存率为29.5%,阴性患者的2年生存率为50.0%,差异有统计学意义(P=0.002)。COX统计结果显示,抑癌基因ADAMTS9甲基化状态是预测肝细胞癌患者术后生存期预后的独立因素(P=0.013)。结论 :抑癌基因ADAMTS9启动子区域的异常甲基化可能参与了肝细胞癌的形成,并能在一定程度上反映肝细胞癌的进展情况,可作为预测术后肝细胞癌患者生存期预后的独立影响因子。
OBJECTIVE: To detect the methylation status of a disintegrin-like and metalloprotease with thromobospondin type 1 motif 9 (ADAMTS 9) in hepatocellular carcinoma (HCC) with tumor suppressor gene thrombin-sensitive protein- To investigate the relationship between the methylation of ADAMTS 9 gene and the occurrence, progression and prognosis of hepatocellular carcinoma. Methods: 132 cases of hepatocellular carcinoma (HCC), 132 cases of paracancerous cirrhosis tissues and 15 cases of normal liver tissues were collected. Methylation-specific polymerase chain reaction (MSP) was used to detect ADAMTS 9 gene Methylation status. Combined with the clinicopathological data and survival time of patients, the value of ADAMTS 9 gene methylation status and occurrence and prognosis of hepatocellular carcinoma was observed. Results: The methylation status of ADAMTS9 gene was not detected in normal liver tissue. The positive rate of ADAMTS9 methylation in hepatocellular carcinoma was 66.67%. The positive rate of methylation of ADAMTS9 gene in adjacent liver cirrhosis (29.55%). Statistical analysis showed that there was a significant difference in methylation positive rates among the three groups (χ2 = 49.918, P = 0.000). According to the clinicopathological data, the positive rate of methylation (78.72%) in patients with portal vein tumor thrombus was higher than that in patients without portal vein tumor thrombus (60.00%) (P = 0.029). The positive rate of methylation in stage Ⅰ ~ Ⅱ cancer patients was higher than that in stage Ⅲ ~ Ⅳ cancer patients, the difference was statistically significant (P = 0.008). Survival analysis showed that the 2-year survival rate of methylation-positive ADAMTS9 gene was 29.5%, and the 2-year survival rate of negative patients was 50.0%, the difference was statistically significant (P = 0.002). The COX statistical results showed that the methylation status of the suppressor gene ADAMTS9 was an independent predictor of the prognosis of patients with hepatocellular carcinoma (P = 0.013). CONCLUSION: Aberrant methylation of the suppressor gene ADAMTS9 promoter region may be involved in the formation of hepatocellular carcinoma, and to a certain extent reflect the progress of hepatocellular carcinoma, which can be used as a prognostic indicator for prognosis of patients with postoperative hepatocellular carcinoma Independent influence factor.