Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, China.
J Gastroenterol Hepatol. 2020 Aug;35(8):1347-1354. doi: 10.1111/jgh.15021. Epub 2020 Mar 7.
DNA methylation is an important epigenetic modification that can promote the development of various cancers. The STAT1 and SOCS3 have been observed to be hypermethylated in tumor tissues and peripheral blood. This study aimed to explore the relationship between the methylation status of the STAT1 and SOCS3 in peripheral blood and gastric cancer (GC).
This hospital-based case-control study involved 372 patients with GC and 379 controls. The methylation status of the STAT1 and SOCS3 was semiquantitatively determined using the methylation-sensitive high-resolution melting method. Logistic regression analysis was used to analyze the relationship between the STAT1 and SOCS3 methylation status and GC susceptibility. Moreover, propensity scores were used to control confounding factors.
Compared with negative methylation, the positive methylation of SOCS3 significantly increased the risk of GC (OR = 1.820, 95% CI: 1.247-2.658, P = 0.002). This trend was also found via stratified analysis, and methylation positivity of the SOCS3 significantly increased the risk of GC in the < 60 years group, in the ≥ 60 years group, and in the positive Helicobacter pylori infection group (OR = 1.654, 95% CI: 1.029-2.660, P = 0.038; OR = 1.957, 95% CI: 1.136-3.376, P = 0.016; OR = 2.084, 95% CI: 1.270-3.422, P = 0.004, respectively). Additionally, no significant association was found between STAT1 methylation and GC risk (OR = 0.646, 95% CI: 0.363-1.147, P = 0.135). This study found that the interaction between the methylation status of STAT1 and SOCS3 and environmental factors did not have an impact on GC risk.
SOCS3 methylation may serve as a new potential biomarker for GC susceptibility.
DNA 甲基化是一种重要的表观遗传修饰，可促进多种癌症的发展。已经观察到 STAT1 和 SOCS3 在肿瘤组织和外周血中发生高甲基化。本研究旨在探讨外周血中 STAT1 和 SOCS3 的甲基化状态与胃癌（GC）之间的关系。
本项基于医院的病例对照研究纳入了 372 例 GC 患者和 379 例对照。采用甲基化敏感高分辨率熔解法半定量检测 STAT1 和 SOCS3 的甲基化状态。采用 logistic 回归分析探讨 STAT1 和 SOCS3 甲基化状态与 GC 易感性的关系。此外，还采用倾向评分控制混杂因素。
与阴性甲基化相比，SOCS3 的阳性甲基化显著增加了 GC 的发病风险（OR=1.820，95%CI：1.247-2.658，P=0.002）。这种趋势在分层分析中也得到了验证，SOCS3 的阳性甲基化显著增加了<60 岁组、≥60 岁组和阳性幽门螺杆菌感染组 GC 的发病风险（OR=1.654，95%CI：1.029-2.660，P=0.038；OR=1.957，95%CI：1.136-3.376，P=0.016；OR=2.084，95%CI：1.270-3.422，P=0.004）。此外，未发现 STAT1 甲基化与 GC 风险之间存在显著关联（OR=0.646，95%CI：0.363-1.147，P=0.135）。本研究发现，STAT1 和 SOCS3 甲基化状态与环境因素之间的相互作用不会影响 GC 风险。
SOCS3 甲基化可能成为 GC 易感性的新潜在生物标志物。
