早期胃癌采用内镜治疗，但由于存在异时性胃病变（MGL）的风险，患者需要进行监测。表观遗传改变，特别是 MIR124-3、MIR34b/c、NKX6-1、EMX1、MOS 和 CDO1 等基因中的异常 DNA 甲基化，已被确定为亚洲人群中 MGL 的有希望的生物标志物。我们的目的是确定这些变化是否可以预测中危白种人患者的 MGL 风险。这项病例队列研究包括 36 名发生 MGL 的患者，与 48 名在同一时间范围内没有 MGL 证据的患者（对照）相匹配。使用从原发病变附近的正常粘膜提取的 DNA 进行多重定量甲基化特异性 PCR。使用 Kaplan-Meier 和 Cox 比例风险模型分析评估进展为 MGL 的总体风险。在 77 个样本中成功分析了 MIR124-3、MIR34b/c 和 NKX6-1。在患有 MGL 的个体中检测到 MIR124-3 高甲基化（相对定量为 78.8 对比对照组的 50.5，p = 0.014），特别是在女性和幽门螺杆菌阴性患者中（分别为 p = 0.021 和 p = 0.0079）。这一发现进一步与显着增加的 MGL 发生风险相关（aHR = 2.31，95% CI 1.03-5.17，p = 0.042）。同样，NKX6-1 在同时病变的患者中被发现高度甲基化（相对定量为 7.9 vs 对照组的 0.0，p = 0.0026）。结合这两个基因的基于分子的甲基化模型与 MGL 发展风险增加三倍显着相关（aHR = 3.10，95% CI 1.07-8.95，p = 0.037）。这项初步研究揭示了 MIR124-3 和 NKX6- 之间的关联。 1 西方人群中的高甲基化和 MGL 的发展。这些发现可能代表减轻负担和更环保的患者护理方法。© 2024。作者。

Early gastric cancer is treated endoscopically, but patients require surveillance due to the risk of metachronous gastric lesions (MGLs). Epigenetic alterations, particularly aberrant DNA methylation in genes, such as MIR124-3, MIR34b/c, NKX6-1, EMX1, MOS and CDO1, have been identified as promising biomarkers for MGL in Asian populations. We aimed to determine whether these changes could predict MGL risk in intermediate-risk Caucasian patients.This case-cohort study included 36 patients who developed MGL matched to 48 patients without evidence of MGL in the same time frame (controls). Multiplex quantitative methylation-specific PCR was performed using DNA extracted from the normal mucosa adjacent to the primary lesion. The overall risk of progression to MGL was assessed using Kaplan-Meier and Cox proportional hazards model analyses.MIR124-3, MIR34b/c and NKX6-1 were successfully analyzed in 77 samples. MIR124-3 hypermethylation was detected in individuals who developed MGL (relative quantification 78.8 vs 50.5 in controls, p = 0.014), particularly in females and Helicobacter pylori-negative patients (p = 0.021 and p = 0.0079, respectively). This finding was further associated with a significantly greater risk for MGL development (aHR = 2.31, 95% CI 1.03-5.17, p = 0.042). Similarly, NKX6-1 was found to be hypermethylated in patients with synchronous lesions (relative quantification 7.9 vs 0.0 in controls, p = 0.0026). A molecular-based methylation model incorporating both genes was significantly associated with a threefold increased risk for MGL development (aHR = 3.10, 95% CI 1.07-8.95, p = 0.037).This preliminary study revealed an association between MIR124-3 and NKX6-1 hypermethylation and the development of MGL in a Western population. These findings may represent a burden reduction and a greener approach to patient care.© 2024. The Author(s).