Phosphorylated STAT3 expression linked to SOCS3 methylation is associated with proliferative ability of gastric mucosa in patients with early gastric cancer
Phosphorylated STAT3 expression linked to SOCS3 methylation is associated with proliferative ability of gastric mucosa in patients with early gastric cancer
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DOI：
10.3892/ol.2020.11462
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发表时间：
2020-03
期刊：
影响因子：
2.9
通讯作者：
H. Fukui;J. Watari;Xinxing Zhang;Ying Ran;T. Tomita;T. Oshima;S. Hirota;H. Miwa
中科院分区：
文献类型：
--
作者：
H. Fukui;J. Watari;Xinxing Zhang;Ying Ran;T. Tomita;T. Oshima;S. Hirota;H. Miwa
使用根除疗法消除幽门螺杆菌（H. pylori）后，胃粘膜可能会出现胃癌（GC）。细胞因子信号传导是胃癌发生和进展的关键机制，STAT3 信号传导可能在胃炎相关肿瘤发生中发挥核心作用。在本研究中，检查了细胞因子信号传导抑制因子 3 (SOCS3) 甲基化，作为早期 GC 患者非肿瘤性胃粘膜 (non-NGM) 中磷酸化 (p-)STAT3 表达的激活剂。使用甲基化特异性 PCR 在患有或不患有早期 GC 的非 NGM 患者中分析 SOCS3 基因启动子的甲基化状态。在幽门螺杆菌根除前后的非 NGM 早期 GC 中，通过免疫组织化学方法研究了 p-STAT3 和 Ki67 的表达水平。在非 NGM 中，17/51 (33.3%) 的早期 GC 患者检测到 SOCS3 启动子甲基化。在这些患者中，Ki67 和 p-STAT3 的非 NGM 标记指数均显着高于无 SOCS3 甲基化的早期 GC 患者。在早期 GC 患者的非 NGM 中，Ki67 和 p-STAT3 表达水平之间存在显着相关性。在无SOCS3甲基化的早期GC患者中，根除H. pylori后，非NGM中Ki67和p-STAT3的标记指数均显着降低，而在有SOCS3甲基化的早期GC患者中未观察到这种变化。 SOCS3 甲基化与早期 GC 患者非 NGM 中持续的 p-STAT3 过表达和上皮细胞增殖增强相关。
Gastric cancers (GCs) may develop in the gastric mucosa after elimination of Helicobacter pylori (H. pylori) using eradication therapy. Cytokine signaling is a key mechanism underlying GC development and progression, and STAT3 signaling may serve a central role in gastritis-associated tumorigenesis. In the present study, suppressor of cytokine signaling 3 (SOCS3) methylation was examined, as an activator of phosphorylated (p-)STAT3 expression in the non-neoplastic gastric mucosa (non-NGM) of patients with early GC. The methylation status of the SOCS3 gene promoter was analyzed using methylation-specific PCR in the non-NGM of patients with or without early GC. Expression levels of p-STAT3 and Ki67 were investigated immunohistochemically in non-NGM with early GC before and after H. pylori eradication. In non-NGM, SOCS3 promoter methylation was detected in 17/51 patients (33.3%) with early GC. In those patients, the non-NGM labeling indices of both Ki67 and p-STAT3 were significantly higher compared with that in patients with early GC without SOCS3 methylation. A significant correlation between Ki67 and p-STAT3 expression levels was demonstrated in the non-NGM of patients with early GC. In patients with early GC without SOCS3 methylation, the labeling indices of both Ki67 and p-STAT3 in non-NGM were significantly reduced after H. pylori eradication, whereas no such change was observed in patients with early GC with SOCS3 methylation. SOCS3 methylation is associated with continuous p-STAT3 overexpression and enhanced epithelial cell proliferation in non-NGM of patients with early GC.