RASSF1A和APC基因启动子区甲基化与前列腺癌的关系

Association of methylation status of RASSF1A and APC promoters with prostate cancer

目的研究Ras相关区域家族1A(Ras association domain family 1 isoform A,RASSF1A)及结肠腺瘤性息肉病(adenomatosis polyposis coli,APC)基因启动子区CpG甲基化及与前列腺癌(PCa)之间的关系,探索PCa早期诊断的检测方法。方法收集60例PCa和40例前列腺增生(BPH)病例的组织标本及其相关的临床指标。应用亚硫酸氢盐修饰后测序法检测PCa组织及BPH组织中RASSF1A、APC基因启动子区CpG甲基化情况。结果 PCa组RASSF1A、APC基因CG位点甲基化率高于BPH组(60.8%vs 14%,48.84%vs 1.19%,P<0.05);基因甲基化率与PSA、Gleason评分、病理分期和PCa危险分期关系密切(P<0.01);RASSF1A及APC基因甲基化联合检测用于判断PCa及BPH的敏感度和特异度是95.74%和82.9%。结论 RASSF1A、APC基因启动子区甲基化与PCa发生及发展有关,其甲基化率的变化与PCa的危险分期关系密切。检测前列腺组织中相关基因甲基化状态,有望成为诊断早期PCa的一种方法。

Objective To investigate the promoter methylation status of Ras association domain family 1 isoform A（RASSF1A） and adenomatosis polyposis coli promoter（APC） and its association with prostate cancer（PCa）,so as to pave a way for early diagnosis of Pca.Methods The prostatic tissues and clinical data were collected from 60 patients with prostate cancer and 40 patients with benign prostatic hyperplasia（BPH） tissues.Bisulphite Sequencing PCR was used to detect the promoter CpG methylation of RASSF1A and APC genes.Results The methylation rates of promoter CG sites of RASSF1A and APC genes in Pca group were significantly higher whan those in the BPH group（RASSF1A： 60.8% vs 14%;APC： 48.84% vs 1.19%,P0.05）.The methylation rates in RASSF1A and APC genes were significantly associated with PSA,Gleason score,pathologic stage and risk classification of PCa（P0.01）.Combined detection of methylation status of RASSF1A and APC genes yielded a sensitivity of 95.74% and a specificity of 82.90% in differential diagnosis of PCa and BPH.Conclusion The promoter methylation of RASSF1A and APC genes are associated with the development and progression of PCa,and the changes of methylation rate is closely associated with risk classification of PCa.Combined detection of methylation in RASSF1A and APC genes may be a promising method for early diagnosis of prostate carcinoma.