Purpose Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). Materials and Methods We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. Results CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively). Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival. Conclusions CLDN18.2 expression was reduced in patients with PM but significantly intact in those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.

中文翻译：

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CLDN18.2在转移性弥漫型胃癌中表达的临床意义

目的紧密连接蛋白 claudin-18 (CLDN18.2) 的异构体 2 是胃癌治疗的潜在靶点。针对 CLDN18.2 的治疗已在胃癌中显示出有希望的结果。我们研究了 CLDN18.2 和其他细胞粘附连接分子（Rho GTP 酶激活蛋白 [RhoGAP] 和 E-钙粘蛋白）在转移性弥漫型胃癌 (mDGC) 中的临床意义。材料和方法 我们使用双重免疫荧光和定量数据分析对 2015 年 3 月至 2017 年 2 月期间接受一线铂类化疗的 77 名连续 mDGC 患者的 H 评分进行了评估 CLDN18.2、RhoGAP 和 E-cadherin 表达。结果 诊断时腹膜转移（PM）患者CLDN18.2和E-cadherin的表达明显低于无PM患者（P=0.010和0.013，分别），而从诊断到死亡从未发生 PM 的患者显着高于那些发生 PM 的患者（分别为 P = 0.001 和 0.003）。同时，骨转移患者CLDN18.2和E-cadherin的表达水平显着高于无骨转移患者（分别为P=0.010和0.001）。此外，我们发现 CLDN18.2 和 E-cadherin (P<0.001)、RhoGAP 和 CLDN18.2 (P=0.004) 以及 RhoGAP 和 E-cadherin (P=0.001) 的表达呈正相关。相反，CLDN18.2、RhoGAP 和 E-cadherin 的表达与化疗反应和生存率无关。结论 CLDN18.2 表达在 PM 患者中降低，但在骨转移患者中明显完整。此外，CLDN18。