新疆维吾尔族妇女子宫颈癌DBC1基因启动子甲基化分析

doi:10.3969/j.issn.1007-3969.2016.03.002

中国癌症杂志 ›› 2016, Vol. 26 ›› Issue (3): 208-214.doi: 10.3969/j.issn.1007-3969.2016.03.002

新疆维吾尔族妇女子宫颈癌DBC1基因启动子甲基化分析

武　丹¹，杨　昕²，朱君玲³，王红英⁴，李洪涛¹，潘　欢¹，何鸿昌¹，任显显¹，潘泽民¹

1. 石河子大学新疆地方与民族高发病教育部重点实验室，石河子大学医学院生物化学教研
室，新疆石河子 832002 ；
2. 新疆医科大学自治区中医医院病理科，新疆乌鲁木齐 830000 ；
3. 喀什地区第一人民医院病理科，新疆喀什 844000 ；
4. 新疆医科大学基础医学院微生物学教研室，新疆乌鲁木齐 830011

出版日期:2016-03-30 发布日期:2016-06-13
通信作者: 潘泽民　E-mail:panteacher89@sina.com
基金资助:
兵团国际科技合作项目(2013BC003)；国家科技支撑计划(“十二五”计划)(2013BAI05B0503)；国家自然科学基金项目(30860302，30660193)；石河子大学重大科技攻关计划项目(gxjs2013-zdgg05)；高层次人才科研启动资金专项(RCZX201333)。

Analysis of DBC1 gene promoter methylation in cervical cancer tissues of Uyghur women in Xinjiang

WU Dan¹, YANG Xin², ZHU Junling³, WANG Hongying⁴, LI Hongtao¹, PAN Huan¹, HE Hongchang¹, REN Xianxian¹, PAN Zemin¹

1.Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Department of Biochemistry and Molecular Biology, School of Medicine, Shihezi University, Shihezi 832002, Xinjiang Uygur Autonomous Region, China; 2. Department of Pathology, Chinese Medicine Hospital of Autonomous Region, Xinjiang Medical University, Urumqi 830000, Xinjiang Uygur Autonomous Region, China; 3. Department of Pathology, the First People Hospital of Kashgar, Kashgar 844000, Xinjiang Uygur Autonomous Region, China; 4. Department of Microbiology, College of Basic Medicine, Xinjiang Medical University, Urumqi 830011, Xinjiang Uygur Autonomous Region, China

Published:2016-03-30 Online:2016-06-13
Contact: PAN Zemin E-mail: panteacher89@sina.com

摘要/Abstract

摘要： 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mRNA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mRNA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。

关键词: 子宫颈癌, DBC1基因甲基化, HPV16/18, 基因表达

Abstract: Background and purpose: In recent years, epigenetics research has become a new direction of cancer research. A large number of results have shown that the abnormal changes of epigenetic modifications have close connection with cancer. Genome-wide epigenetic modifications have become new markers for cancer. This study aimed to investigate the methylation of the promoter of DBC1 gene in cervical cancer tissues of Uyghur women in Xinjiang, to explore the correlation between the gene methylation and the infection of HPV, and to evaluate whether it can be used as a tool with high sensitivity and specificity for cervical cancer screening. Methods: This study detected the infection of HPV16, 18 in 43 normal cervical tissues, 35 cervical intraepithelial neoplasia tissues and 54 cervical cancer tissues using the polymerase chain reaction (PCR) method. The methylation of the promoter of DBC1 gene in above-mentioned tissues was detected by the methylation-specific PCR method. The expression of DBC1 at mRNA level was measured by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) in 10 methylation-negative normal cervical tissues and 10 methylation-positive cervical cancer tissues. Results: In normal cervical tissues, CIN tissues and cervical cancer tissues, the infection ratios of HPV16 were 18.6%, 34.3% and 68.5%, respectively; the infection ratios of HPV18 were 2.3%, 8.6% and 16.7%, respectively; and the methylation ratios of DBC1 gene were 23.3%, 40.0%, 87.0%, respectively. In 79 highgrade squamous intraepithelial lesions (CINⅡ and Ⅲ) and cervical cancer tissues, 50 of 79 were infected with HPV16/18, while 29 of 79 were negative. The methylation ratio of DBC1 gene was 88.0% in HPV16/18 infection positive group while the methylation ratio was 55.2% in negative group (P<0.05). The expression of DBC1 gene at mRNA level in 10 methylation-positive cervical cancer tissues was significantly lower than that in the 10 methylation-negative normal cervical tissues (P<0.05). Conclusion: The methylation of DBC1 gene may become a molecular marker to detect cervical cancer of Uyghur women in Xinjiang. DBC1 gene methylation combined with HPV16/18 infection test can be used to aid diagnosis of cervical cancer.

Key words: Cervical cancer, DBC1 gene methylation, HPV16/18, Gene expression

武　丹,杨　昕,朱君玲,等. 新疆维吾尔族妇女子宫颈癌DBC1基因启动子甲基化分析[J]. 中国癌症杂志, 2016, 26(3): 208-214.

WU Dan, YANG Xin, ZHU Junling, et al. Analysis of DBC1 gene promoter methylation in cervical cancer tissues of Uyghur women in Xinjiang[J]. China Oncology, 2016, 26(3): 208-214.

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新疆维吾尔族妇女子宫颈癌DBC1基因启动子甲基化分析

Analysis of DBC1 gene promoter methylation in cervical cancer tissues of Uyghur women in Xinjiang

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