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目的:探讨凝血栓蛋白1(THBSl)基因启动子CpG岛异常甲基化,蛋白表达与大肠腺癌及其临床病理特征的关联,并分析THBS1基因蛋白表达与其甲基化的相关性.方法:应用免疫组化和甲基化特异性PCR技术分别检测大肠腺癌94例及其残端正常黏膜组织中,THBS1基因启动子CpG岛甲基化和蛋白表达情况.结果:大肠腺癌和癌旁组织中,THBS1蛋白表达率(61.7%vs77.7%),CpG岛甲基化率(25.5%vs11.7%)的差异均有显著性(前者X2=5.67,P=0.017,后者X2=5.93,P=0.015),老年患者肿瘤组织中THBS1蛋白表达率明显低于非老年患者(48.8%vs72.5%,X2=5.55,P=0.018),甲基化率明显高于非老年患者(37.2%vs15.7%,X2=5.68,P=0.017),直径≥3cm的肿瘤组织中THBS1蛋白表达率显著低于直径<3cm的肿瘤(53.4%vs75.0%,X2=4.37,P=0.037),甲基化率显著高于直径<3cm的肿瘤(32.6%vs13.9%,X=4.16,P=0.041),C期和D期肿瘤组织中THBS1蛋白表达率显著低于A期或B期肿瘤(44.4%vs73.3%,72.1%,X2=7.36,v=2,P=0.025)、甲基化率显著高于A期或B期肿瘤(41.7%vs13.3%,16.3%,X2=8.04,v=2,P=0.018),大肠腺癌THBS1蛋白阴性与阳性表达的组织之间,启动子CpG岛甲基化率的差异有显著性(0%vs66.7%,P<0.0005).结论:THBS1基因异常甲基化是其蛋白表达缺失的主要原因之一,并在大肠癌的发生发展中起重要作用.
Objective: To investigate the relationship between CpG island methylation, protein expression and the clinicopathological features of CpG island in thrombolytic protein 1 (THBS1) promoter and the correlation between THBS1 gene methylation and methylation.Methods: Immunohistochemistry and methylation-specific PCR were used to detect methylation and protein expression of CpG island of THBS1 promoter in 94 cases of colorectal adenocarcinoma and its normal mucosa, respectively.Results: (61.7% vs77.7%) and CpG island methylation (25.5% vs11.7%) were significantly different between the two groups (X2 = 5.67, P = 0.017, X2 = 5.93, P = 0.015). The expression of THBS1 protein in elderly patients was significantly lower than that in non-elderly patients (48.8% vs72.5%, X2 = 5.55, P = 0.018) 37.2% vs15.7%, X2 = 5.68, P = 0.017). The expression of THBS1 protein was significantly lower in tumors with diameter≥3cm than those with diameter <3cm (53.4% vs75.0%, X2 = 4.37, P = ), The methylation rate was significantly higher than that of tumors with a diameter of less than 3 cm (32.6% vs13.9%, X = 4.16, P = 0.041). The expression rates of THBS1 protein in stage C and stage D were significantly lower than those in stage A or B Stage tumors (44.4% vs 73.3%, 72.1%, X. The methylation rate was significantly higher in patients with stage A or B tumors (41.7% vs13.3%, 16.3%, X2 = 8.04, v = 2, P = 0.018) The methylation rate of CpG island of promoter was significantly different between the negative and the positive tissues of THBS1 (0% vs66.7%, P <0.0005) .Conclusion: Abnormal methylation of THBS1 gene is One of the main reasons for the loss of protein expression, and plays an important role in the occurrence and development of colorectal cancer.