Wettergren Yvonne, Rolny Peter, Lindegren Helena, Odin Elisabeth, Rotter Sopasakis Victoria, Keane Simon, Ejeskär Katarina
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Surgery, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
Mol Cell Oncol. 2025 May 10;12(1):2503069. doi: 10.1080/23723556.2025.2503069. eCollection 2025.
The genes MutL Homolog 1 (), O6-methylguanine-DNA methyltransferase (), and cyclin-dependent kinase inhibitor are commonly downregulated by hypermethylation in colorectal cancer. Long interspersed nucleotide element 1 (LINE-1) can be used as marker for global hypomethylation. This study compared , , , and LINE-1 methylation with gene expression in colon tumors, matched non-cancerous mucosa, and control mucosa to identify signs of premalignancy. Tissues were obtained from 20 colon cancer patients and 40 controls. CpG site methylation was quantified by pyrosequencing, expression by qPCR, and MSI/ status by fragment analysis and droplet digital PCR. , , and methylation was increasingly higher in control mucosa, non-cancerous mucosa, and tumors. expression was lower in tumors compared to non-cancerous mucosa but higher compared to control mucosa. Tumoral LINE-1 methylation correlated negatively with ( = -0.51, = .021) and p16INK4a ( = -0.55, = .012) methylation, but positively ( = 0.74, = .0002) with expression. A SNP (rs3814960 C>T) was associated with methylation, expression, and MSI/ status. Aberrant methylation of tumor suppressor genes in colon mucosa could be an early cancer risk marker. Control mucosa is a more reliable reference than non-cancerous mucosa when identifying premalignant changes. Extended studies will evaluate the possible association between rs3814960 and cancer susceptibility. : NCT03072641.
错配修复蛋白MutL同源蛋白1（）、O6-甲基鸟嘌呤-DNA甲基转移酶（）和细胞周期蛋白依赖性激酶抑制剂在结直肠癌中通常因高甲基化而下调。长散在核元件1（LINE-1）可作为全基因组低甲基化的标志物。本研究比较了结直肠肿瘤、配对的非癌黏膜和对照黏膜中、、和LINE-1的甲基化与基因表达情况，以确定癌前病变迹象。组织取自20例结肠癌患者和40例对照。通过焦磷酸测序对CpG位点甲基化进行定量，通过qPCR检测基因表达，并通过片段分析和液滴数字PCR检测微卫星不稳定性（MSI）/状态。在对照黏膜、非癌黏膜和肿瘤中，、和的甲基化程度逐渐升高。与非癌黏膜相比，肿瘤中的表达较低，但与对照黏膜相比则较高。肿瘤LINE-1甲基化与（r = -0.51，P = 0.021）和p16INK4a（r = -0.55，P = 0.012）甲基化呈负相关，但与表达呈正相关（r = 0.74，P = 0.0002）。一个单核苷酸多态性（SNP，rs3814960 C>T）与甲基化、表达及MSI/状态相关。结肠黏膜中抑癌基因的异常甲基化可能是早期癌症风险标志物。在识别癌前变化时,对照黏膜比非癌黏膜是更可靠的参照。进一步的研究将评估rs3814960与癌症易感性之间可能存在的关联。试验注册号：NCT03072641。
