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结直肠癌、癌前病变及癌旁正常黏膜中LINE-1 DNA甲基化分析

Analysis of LINE-1 DNA Methylation in Colorectal Cancer, Precancerous Lesions, and Adjacent Normal Mucosa.

作者信息

Kildusiene Inga, Rynkeviciene Ryte, Kaceniene Auguste, Miknaite Rima, Suziedelis Kestutis, Smailyte Giedre

机构信息

Institute of Biosciences, Life Sciences Center, Vilnius University, LT-03101 Vilnius, Lithuania.

Laboratory of Cancer Epidemiology, National Cancer Institute, P. Baublio 3B, LT-08406 Vilnius, Lithuania.

出版信息

Medicina (Kaunas). 2025 Jul 10;61(7):1243. doi: 10.3390/medicina61071243.

Abstract

: Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide. Genetic and epigenetic changes, especially DNA methylation alterations, are key in CRC development. hypomethylation marks global DNA methylation loss and genomic instability, making it a potential early CRC biomarker. This study investigates the methylation status of in colorectal adenocarcinoma, precancerous lesions (tubular and serrated adenomas), and the surrounding normal mucosa, aiming to elucidate its role as an epigenetic marker in early colorectal tumorigenesis. : Paired lesion and normal tissue samples from 66 patients were analyzed for LINE-1 methylation at three CpG sites using bisulfite pyrosequencing. Adenocarcinomas and tubular adenomas showed significant hypomethylation, especially at loci A and B, while serrated adenomas exhibited no significant differences. : hypomethylation is associated with colorectal tumorigenesis, with distinct patterns observed between tubular and serrated adenomas, indicating distinct pathways forming and progressing specific adenomas. These findings support the potential of methylation as an early epigenetic biomarker for CRC risk stratification and highlight the need for further research into its clinical utility.

摘要

结直肠癌(CRC)是全球癌症发病和死亡的主要原因。基因和表观遗传变化,尤其是DNA甲基化改变,在CRC发展中起关键作用。低甲基化标志着整体DNA甲基化缺失和基因组不稳定,使其成为潜在的早期CRC生物标志物。本研究调查了在结直肠腺癌、癌前病变(管状和锯齿状腺瘤)及周围正常黏膜中的甲基化状态,旨在阐明其作为早期结直肠肿瘤发生中表观遗传标志物的作用。:使用亚硫酸氢盐焦磷酸测序法分析了66例患者的配对病变组织和正常组织样本在三个CpG位点的LINE-1甲基化情况。腺癌和管状腺瘤显示出显著的低甲基化,尤其是在A和B位点,而锯齿状腺瘤未显示出显著差异。:低甲基化与结直肠肿瘤发生相关,管状腺瘤和锯齿状腺瘤之间观察到不同模式,表明形成和进展特定腺瘤的途径不同。这些发现支持了甲基化作为CRC风险分层早期表观遗传生物标志物的潜力,并强调了对其临床应用进行进一步研究的必要性。

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