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炎症性肠病患者发育异常中的甲基化模式。

Methylation patterns in dysplasia in inflammatory bowel disease patients.

作者信息

Rosa Isadora, Silva Patrícia, da Mata Sara, Magro Fernando, Carneiro Fátima, Peixoto Armando, Silva Marco, Sousa Helena T, Roseira Joana, Parra José, Barosa Rita, Vieira Ana, Brito Maria José, Lago Paula, Coelho André, Moleiro Joana, Pereira da Silva João, Fonseca Ricardo, Albuquerque Cristina, Dias Pereira A

机构信息

Gastroenterology Department, Instituto Português de Oncologia de Lisboa, Francisco Gentil, EPE, Lisboa, Portugal.

Molecular Pathobiology Investigation Unit, Instituto Português de Oncologia de Lisboa, Francisco Gentil, EPE, Lisboa, Portugal.

出版信息

Scand J Gastroenterol. 2020 Jun;55(6):646-655. doi: 10.1080/00365521.2020.1766552. Epub 2020 May 26.

Abstract

Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBD patients is difficult. Some data favors the importance of abnormal DNA methylation in IBD-related carcinogenesis. We aimed to define methylation patterns in patients with colonic cancer or dysplasia diagnosis following an IBD diagnosis. Multicentric cross-sectional study-91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification. Mean age at IBD diagnosis: 42 ± 16 years;at dysplasia diagnosis: 56 ± 14 years. Twenty-ninepatients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis ( = .003) and at dysplasia/cancer diagnosis ( = .039). Promoter methylation of genes was significantly associated to dysplasia/cancer; methylation of was significantly associated to IBD-related dysplasia/cancer. Promoter methylation of genes was significantly associated to active IBD. Methylation analysis, namely of , may contribute to the classification of dysplastic lesions in IBD- to be further tested in prospective studies.

摘要

累及结肠的炎症性肠病(IBD)会增加结直肠癌风险。然而,区分IBD患者中与IBD相关的发育异常和散发性发育异常很困难。一些数据支持异常DNA甲基化在IBD相关致癌过程中的重要性。我们旨在确定IBD诊断后被诊断为结肠癌或发育异常的患者的甲基化模式。多中心横断面研究——纳入了9例IBD相关发育异常/癌症患者和26例IBD及散发性发育异常/癌症患者的结肠黏膜样本,共91份,有或无发育异常。通过甲基化特异性多重连接依赖探针扩增技术研究了67个基因启动子区域CpG岛的甲基化模式。IBD诊断时的平均年龄:42±16岁;发育异常诊断时的平均年龄:56±14岁。29例患者患有溃疡性结肠炎。25例患者至少有1个内镜下描述为腺瘤样的病变,4例至少有1个非腺瘤样病变,3例患有癌症,3例在平坦黏膜中有发育异常。没有患者同时有腺瘤样和非腺瘤样病变。IBD相关病变患者在IBD诊断时(P = 0.003)和发育异常/癌症诊断时(P = 0.039)明显更年轻。基因启动子甲基化与发育异常/癌症显著相关;[具体基因]的甲基化与IBD相关发育异常/癌症显著相关。[具体基因]启动子甲基化与活动期IBD显著相关。甲基化分析,即[具体基因]的甲基化分析,可能有助于IBD发育异常病变的分类——有待在前瞻性研究中进一步验证。

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