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基因启动子甲基化在炎症和宫颈上皮内瘤变中的作用。

The Role of and Promoter Methylation in Inflammation and Cervical Intraepithelial Neoplasia.

机构信息

Division of Oncology, Jessenius Faculty of Medicine, Biomedical Center Martin, Comenius University in Bratislava, Martin, Slovakia.

Bioinformatic Unit, Jessenius Faculty of Medicine, Biomedical Center Martin, Comenius University in Bratislava, Martin, Slovakia.

出版信息

Genet Test Mol Biomarkers. 2020 May;24(5):256-263. doi: 10.1089/gtmb.2019.0188. Epub 2020 Apr 20.

DOI:10.1089/gtmb.2019.0188
PMID:32311274
Abstract

This study investigated the presence of human papillomavirus (HPV) infection and the methylation status of the promoters of the cell adhesion molecule 1 () gene and T lymphocyte maturation associated protein () gene in patients with cervicitis/inflammation and cervical intraepithelial neoplasia (CIN). Cervical specimens ( = 47) were collected from women with normal cervical cytology ( = 21) and those with cervical abnormalities ( = 26). The presence of HPV infection was confirmed by an HPV DNA test and an HPV mRNA test (Aptima HPV test). Methylation levels of the and promoters were evaluated by pyrosequencing. Compared with the HPV DNA test, the Aptima HPV test improved specificity from 57% to 70% for the detection of inflammation and/or CIN type 1 (CIN1) or more advanced conditions (CIN1+). The methylation level of the and promoters was 1.5 times higher in inflammatory samples, compared with normal cervical cytology ( < 0.05). Selected 5'-C-phosphate-G-3' islands within the promoters of the and genes were differentially methylated in the inflammatory samples compared with the CIN samples. These results suggested that methylation likely occurred following tissue disruption, and the detection of persistent inflammation might be associated with a higher risk of lesion progression.

摘要

本研究旨在探讨宫颈炎/炎症和宫颈上皮内瘤变(CIN)患者中人类乳头瘤病毒(HPV)感染以及细胞黏附分子 1()基因和 T 淋巴细胞成熟相关蛋白()基因启动子甲基化状态的存在。收集了来自宫颈细胞学正常(n=21)和宫颈异常(n=26)女性的宫颈标本(n=47)。通过 HPV DNA 检测和 HPV mRNA 检测(Aptima HPV 检测)证实 HPV 感染的存在。通过焦磷酸测序评估 和 启动子的甲基化水平。与 HPV DNA 检测相比,Aptima HPV 检测提高了对炎症和/或 CIN1 或更高级别病变(CIN1+)检测的特异性,从 57%提高到 70%。与正常宫颈细胞学相比,炎症样本中 基因和 基因启动子的甲基化水平高 1.5 倍(<0.05)。与 CIN 样本相比,炎症样本中 基因和 基因启动子的 5'-C-磷酸-G-3'岛发生了差异甲基化。这些结果表明,甲基化可能发生在组织破坏之后,持续炎症的检测可能与病变进展的风险增加有关。

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