Fukui Hirokazu, Watari Jiro, Zhang Xinxing, Ran Ying, Tomita Toshihiko, Oshima Tadayuki, Hirota Seiichi, Miwa Hiroto
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine Hospital, Nishinomiya, Hyogo 663-8501, Japan.
Department of Surgical Pathology, Hyogo College of Medicine Hospital, Nishinomiya, Hyogo 663-8501, Japan.
Oncol Lett. 2020 May;19(5):3542-3550. doi: 10.3892/ol.2020.11462. Epub 2020 Mar 16.
Gastric cancers (GCs) may develop in the gastric mucosa after elimination of () 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, () 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 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 eradication. In non-NGM, 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 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 methylation, the labeling indices of both Ki67 and p-STAT3 in non-NGM were significantly reduced after eradication, whereas no such change was observed in patients with early GC with methylation. methylation is associated with continuous p-STAT3 overexpression and enhanced epithelial cell proliferation in non-NGM of patients with early GC.
在使用根除疗法消除（）后，胃癌（GCs）可能在胃黏膜中发生。细胞因子信号传导是GC发生和发展的关键机制，而STAT3信号传导可能在胃炎相关的肿瘤发生中起核心作用。在本研究中，检测了（）甲基化，其作为早期GC患者非肿瘤性胃黏膜（non-NGM）中磷酸化（p-）STAT3表达的激活剂。使用甲基化特异性PCR分析有或无早期GC患者的non-NGM中基因启动子的甲基化状态。在根除（）前后，对早期GC患者的non-NGM进行免疫组织化学研究，检测p-STAT3和Ki67的表达水平。在17/51例（33.3%）早期GC患者的non-NGM中检测到启动子甲基化。在这些患者中，与无甲基化的早期GC患者相比，Ki67和p-STAT3的non-NGM标记指数显著更高。在早期GC患者的non-NGM中，Ki67和p-STAT3表达水平之间存在显著相关性。在无甲基化的早期GC患者中，根除（）后non-NGM中Ki67和p-STAT3的标记指数显著降低，而在有甲基化的早期GC患者中未观察到这种变化。甲基化与早期GC患者non-NGM中p-STAT3的持续过表达和上皮细胞增殖增强有关。
