胱硫醚-β-合酶基因启动子区CpG岛甲基化水平与结直肠癌患者临床病理特征的关系

摘要

Objective To explore the association between methylation of cystathionine-beta synthase (CBS) promoter and clinicopathological features in colorectal cancer.Methods Bisulfate sequencing PCR,real-time RT-PCR,and immunohistochemistry were used to investigate the methylation of CpG island in CBS promoter of 95 sporadic colorectal cancers.Software SPSS PASW Statistics was used to analyze the data of the hypermethylation levels in the malignant tissues and the correlation with pathological parameters and clinical outcome.Results Methylation levels in tumor tissue of patients [(64.9 ±14.3) ％] with colorectal cancer were significantly higher than that in normal tissues [(27.5 ±13.1) ％,P <0.001].The CBS mRNA levels in the hypomethylation group (7.22± 1.91) were significantly higher than that in the hypermethylation group (2.78 ±1.12,P <0.01).Univariate analysis showed that age,pT stage,pN stage,liver metastases,pTNM stage,and CBS hypermethylation level significantly correlated with the survival and recurrence rates of colorectal cancer patients (All P <0.05).Multivariate analysis showed that CBS hypermethylation level and liver metastasis were independent factors significantly correlated with the recurrence rate and overall survival of the patients (All P <0.05).Conclusions Our study indicates that methylation of CpG island in CBS promoter is correlated with the occurrence and progression of colorectal cancer and plays a role in its tumorigenesis.It might serve as a useful marker for early diagnosis,targeted therapy and prediction of prognosis in colorectal cancer.%目的 探讨胱硫醚-β-合酶(cystathionine beta synthase,CBS)基因启动子区CpG岛的甲基化水平与结直肠癌患者临床病理特征的相关性.方法 通过结合重亚硫酸盐处理的直接测序、实时定量PCR和免疫组化等技术检测95例散发性结直肠癌患者肿瘤组织中CBS基因启动子区CpG岛的甲基化水平,分析其与结直肠癌患者临床病理特征之间的相关性及其对复发率和生存率的影响.结果 结直肠癌患者肿瘤组织中CBS基因启动子区CpG岛的甲基化水平为(64.9±14.3)％,显著高于正常组织[(27.5±13.1)％,P＜0.001].低甲基化组患者的CBS mRNA水平(7.22±1.91)显著高于高甲基化组(2.78 ±1.12,P＜0.01).单因素分析显示,患者年龄、pT分期、pN分期、肝转移、pTNM分期和CBS基因启动子区CpG岛甲基化水平与结直肠癌患者的预后有关(均P＜0.05).多因素分析显示,CBS基因启动子区CpG岛甲基化水平和肝转移为影响结直肠癌患者预后的独立因素(均P＜0.05).结论 CBS基因启动子区CpG岛的甲基化水平不仅与结直肠癌的发生、发展密切相关,而且可以作为一个有效的肿瘤分子诊断标志物,在结直肠癌早期诊断、靶向治疗和预后判断方面有一定意义.