Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.
Center for Health Technology and Services Research (CINTESIS@RISE), University of Porto, Porto, Portugal.
Clin Epigenetics. 2024 Aug 21;16(1):113. doi: 10.1186/s13148-024-01712-z.
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.
早期胃癌经内镜治疗，但由于存在同时性胃病变（MGL）的风险，患者需要进行监测。在亚洲人群中，已发现表观遗传改变，特别是基因中异常的 DNA 甲基化，如 MIR124-3、MIR34b/c、NKX6-1、EMX1、MOS 和 CDO1，是 MGL 的有前途的生物标志物。我们旨在确定这些变化是否可以预测高加索人群中处于中危的患者的 MGL 风险。
本病例对照研究纳入了 36 例在同一时间段内发生 MGL 的患者，并与 48 例无 MGL 证据的患者（对照组）相匹配。使用从原发性病变相邻的正常黏膜中提取的 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。在发生 MGL 的个体中检测到 MIR124-3 过度甲基化（相对定量 78.8 比对照组中的 50.5，p=0.014），特别是在女性和幽门螺杆菌阴性患者中（p=0.021 和 p=0.0079，分别）。这一发现进一步与 MGL 发展的风险显著增加相关（aHR=2.31，95%CI 1.03-5.17，p=0.042）。同样，在同时性病变患者中发现 NKX6-1 过度甲基化（相对定量 7.9 比对照组中的 0.0，p=0.0026）。纳入这两个基因的基于分子的甲基化模型与 MGL 发展的三倍风险增加显著相关（aHR=3.10，95%CI 1.07-8.95，p=0.037）。
本初步研究揭示了 MIR124-3 和 NKX6-1 过度甲基化与西方人群 MGL 发展之间的关联。这些发现可能代表着减轻负担和对患者护理的绿色方法。
