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目的通过检测新鲜冰冻膀胱癌组织中P14ARF、DAPK、RARβ基因的启动子CpG岛基因的甲基化状态,探讨P14ARF、DAPK、RARβ在膀胱癌发生过程中的作用及诊断意义。方法采用甲基化特异性PCR技术检测48例手术切除的膀胱癌组织和其中13例相应癌旁组织标本、17例非肿瘤患者正常膀胱组织中DAPK、RARβ、P14ARF基因的甲基化情况。结果 48例膀胱癌组织中发现P14ARF基因异常甲基化13例(27.0%),DAPK基因异常甲基化13例(27.0%);RARβ基因异常甲基化44例(91.6%);17例腺性膀胱炎组织中发现P14ARF基因异常甲基化0例,DAPK基因异常甲基化2例(11.7%);RARβ基因异常甲基化3例(17.6%);13例正常膀胱组织中,仅有2例RARβ基因异常甲基化,P14ARF基因、RARβ基因异常甲基化膀胱癌组织与腺性膀胱炎组织差异有统计学意义(P<0.01;P<0.05)。结论 P14ARF、DAPK、RARβ基因异常甲基化与膀胱癌发病密切相关,RARβ基因可作为正常膀胱组织与癌组织鉴别诊断的标志物。
Objective To investigate the role of P14ARF, DAPK and RARβ in the pathogenesis of bladder cancer by detecting the methylation status of CpG island genes of P14ARF, DAPK and RARβ gene in fresh frozen bladder cancer. Methods Methylation-specific PCR was used to detect the methylation status of DAPK, RARβ and P14ARF in 48 cases of resected bladder cancer tissues, 13 cases of paracancerous tissues and 17 cases of normal bladder tissues. Results Thirteen cases (27.0%) had abnormal methylation of P14ARF gene, 13 cases (27.0%) had abnormal methylation of DAPK gene, 44 cases (91.6%) had abnormal methylation of RARβ gene, 17 cases The abnormal methylation of P14ARF gene was found in 0 cases of cystitis, 2 cases of abnormal methylation of DAPK gene (11.7%), 3 cases of abnormal methylation of RARβ gene (17.6%), and 13 cases of normal bladder tissue Two cases of abnormal methylation of RARβ gene, P14ARF gene, abnormal methylation of RARβ gene and cystitis glandularis were statistically different (P <0.01; P <0.05). Conclusion Abnormal methylation of P14ARF, DAPK and RARβ genes is closely related to the pathogenesis of bladder cancer. RARβ gene may serve as a marker for the differential diagnosis between normal bladder tissue and cancer tissue.