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评估p15、p16和E-钙黏蛋白基因的DNA甲基化作为子宫颈早期癌筛查工具的研究

Assessment of DNA Methylation in p15, p16 and E-Cadherin Genes as a Screening Tool for Early Carcinoma Cervix.

作者信息

Banerjee M, Kulhari K, Saha T K

机构信息

All India Institute of Medical Sciences, Jodhpur, India.

Command Hospital Chandigarh, Chandimandir, India.

出版信息

Indian J Clin Biochem. 2020 Oct;35(4):423-429. doi: 10.1007/s12291-019-00837-w. Epub 2019 Jun 12.

DOI:10.1007/s12291-019-00837-w
PMID:33013011
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7502632/
Abstract

Cancer cervix is diagnosed late in women due to anatomical inaccessibility of the area. Hence, a robust screening strategy will help detect carcinoma cervix early which will significantly decrease the mortality and morbidity due to this disease. We evaluated DNA methylation of three tumour suppressor genes p15, p16 and E-Cadherin on cervical smears to assess DNA methylation as a screening tool for detection of early cervical cancer in comparison to PAP smears. DNA was extracted from cervical smears of 20 cases and 30 controls. The DNA was bisulphite modified. Methylation specific PCR (MSP) was performed to assess the methylation status of the promoter region of each of the genes. MSP results were compared with PAP smears to assess the utility of DNA methylation of these genes in screening for cervical cancer. DNA methylation was detected in 55% subjects in p15 gene, 45% in p16 gene and 40% in E-Cadherin gene. This was statistically significant when compared to the controls. DNA methylation of E-Cadherin, and p15 genes as a panel has a sensitivity and specificity of 80% and 90% respectively, which is better than the sensitivity of PAP smear for detection of early cancer cervix. Increased DNA methylation is seen in p15, p16 and E-Cadherin genes in early cancer cervix. p15 and E-Cadherin in combination can be used as a screening tool for detection of early cancer cervix.

摘要

由于该部位解剖结构难以触及,子宫颈癌在女性中往往诊断较晚。因此,强有力的筛查策略将有助于早期发现子宫颈癌,这将显著降低该疾病导致的死亡率和发病率。我们评估了宫颈涂片上三个肿瘤抑制基因p15、p16和E-钙黏蛋白的DNA甲基化情况,以评估DNA甲基化作为与巴氏涂片相比用于检测早期宫颈癌的筛查工具。从20例病例和30例对照的宫颈涂片中提取DNA。对DNA进行亚硫酸氢盐修饰。进行甲基化特异性PCR(MSP)以评估每个基因启动子区域的甲基化状态。将MSP结果与巴氏涂片进行比较,以评估这些基因的DNA甲基化在宫颈癌筛查中的效用。在p15基因中,55%的受试者检测到DNA甲基化;在p16基因中,45%检测到;在E-钙黏蛋白基因中,40%检测到。与对照组相比,这具有统计学意义。作为一个组合,E-钙黏蛋白和p15基因的DNA甲基化敏感性和特异性分别为80%和90%,这优于巴氏涂片检测早期子宫颈癌的敏感性。在早期子宫颈癌中,p15、p16和E-钙黏蛋白基因的DNA甲基化增加。p15和E-钙黏蛋白联合可作为检测早期子宫颈癌的筛查工具。

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本文引用的文献

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Demethylating Agents in the Treatment of Cancer.用于癌症治疗的去甲基化剂
Pharmaceuticals (Basel). 2010 Jul 2;3(7):2022-2044. doi: 10.3390/ph3072022.
2
P16 methylation is an early event in cervical carcinogenesis.P16 甲基化是宫颈癌发生的早期事件。
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Status of p16(INK4a) and E-cadherin gene promoter methylation in Moroccan patients with cervical carcinoma.摩洛哥宫颈癌患者中 p16(INK4a) 和 E-钙黏蛋白基因启动子甲基化的状态。
Oncol Res. 2009;18(4):185-92. doi: 10.3727/096504009790217416.
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[Clinical significance of detection of tumor suppressor genes aberrant methylation in cervical carcinoma tissue].[宫颈癌组织中抑癌基因异常甲基化检测的临床意义]
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p15 (INK4B) and E-cadherin CpG island methylation is frequent in Egyptian acute myeloid leukemia.p15(INK4B)和E-钙黏蛋白CpG岛甲基化在埃及急性髓系白血病中很常见。
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Methylation status of the fragile histidine triad and E-cadherin genes in plasma of cervical cancer patients.宫颈癌患者血浆中脆性组氨酸三联体和E-钙黏蛋白基因的甲基化状态
Int J Gynecol Cancer. 2006 Sep-Oct;16(5):1862-7. doi: 10.1111/j.1525-1438.2006.00669.x.
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Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy.心血管药物肼屈嗪和普鲁卡因胺对肿瘤抑制基因的重新激活作用及其在癌症治疗中的潜在应用。
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Low expression of p27 protein combined with altered p53 and Rb/p16 expression status is associated with increased expression of cyclin A and cyclin B1 in diffuse large B-cell lymphomas.在弥漫性大B细胞淋巴瘤中,p27蛋白低表达联合p53及Rb/p16表达状态改变与细胞周期蛋白A和细胞周期蛋白B1表达增加相关。
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