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背景与目的:近年来,表观遗传学研究已经成为癌症研究的一个新方向。大量研究结果显示,表观遗传修饰的异常改变与癌症有着十分密切的联系,全基因组范围内的表观遗传修饰改变已经成为癌症的新标志。该研究旨在探讨膀胱癌缺失基因1(deleted in bladder cancer 1,DBC1)启动子甲基化与新疆维吾尔族妇女子宫颈癌的关系及与人类乳头瘤病毒(human papillomavirus,HPV)感染的相关性,分析其能否作为高敏感性及特异性的工具用于子宫颈癌筛选。方法:用聚合酶链反应(polymerase chain reaction,PCR)方法对43例正常子宫颈组织、35例子宫颈上皮内瘤样变(cervical intraepithelial neoplasia,CIN)组织以及54例子宫颈癌组织进行HPV16、HPV18感染的检测;运用甲基化特异性PCR方法检测上述组织DBC1基因启动子甲基化状况;采用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)方法检测10例甲基化阴性的正常子宫颈组织和10例甲基化阳性的子宫颈癌组织中DBC1基因m RNA表达情况。结果:正常子宫颈组织、CIN组织及子宫颈癌组织中HPV16的感染率分别为18.6%、34.3%和68.5%;HPV18的感染率分别为2.3%、8.6%和16.7%;DBC1基因发生甲基化率分别为23.3%、40.0%和87.0%;在79例高级别宫颈损伤及子宫颈癌样本中,其中50例HPV16/18感染阳性,29例HPV16/18感染阴性;阳性组中DBC1基因发生甲基化率88.0%,阴性组甲基化率为55.2%(P<0.05);10例甲基化阳性子宫颈癌组织中DBC1基因m RNA表达水平明显低于10例甲基化阴性正常子宫颈组织(P<0.05)。结论:DBC1基因甲基化可能作为新疆维吾尔族妇女子宫颈癌的分子标志物,结合HPV16/18感染检测有助于子宫颈癌的诊断。
Background and purpose: In recent years, epigenetic research has become a new direction of cancer research. Numerous studies have shown that abnormal changes in epigenetic modification are closely linked to cancer, and genome-wide changes in epigenetic modification have become new markers of cancer. The aim of this study was to investigate the relationship between methylation of deleted in bladder cancer 1 (DBC1) promoter and cervical cancer in Uigur women in Xinjiang and its relationship with human papillomavirus (HPV) infection , Analyze whether it can be used as a highly sensitive and specific tool for cervical cancer screening. Methods: 43 cases of normal cervical tissues, 35 cases of cervical intraepithelial neoplasia (CIN) tissues and 54 cases of cervical cancer tissues were infected with HPV16 and HPV18 by polymerase chain reaction (PCR) The methylation status of the promoter of DBC1 gene was detected by methylation-specific PCR method. The expression of DBP1 promoter methylation was detected by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) The expression of DBC1 m RNA in normal cervical tissues and 10 cases of methylation-positive cervical cancer tissues. Results: The infection rates of HPV16 in normal cervical tissues, CIN tissues and cervical cancer tissues were 18.6%, 34.3% and 68.5% respectively. The infection rates of HPV18 were 2.3%, 8.6% and 16.7% In 79 cases of high-grade cervical lesions and cervical cancer samples, 50 cases were positive for HPV16 / 18 and 29 cases were negative for HPV16 / 18, and the positive rate was DBC1 The methylation rate was 88.0% in the negative group and 55.2% in the negative group (P <0.05). The mRNA expression of DBC1 in 10 cases of methylation-positive cervical cancer was significantly lower than that in 10 cases of methylation-negative normal Cervical tissue (P <0.05). Conclusion: Methylation of DBC1 gene may be used as a molecular marker of cervical cancer in Uygur women in Xinjiang. Combined with detection of HPV16 / 18 infection, it is helpful to diagnose cervical cancer.