High RhCG expression predicts poor survival and promotes migration and proliferation of gastric cancer via keeping intracellular alkaline
High RhCG expression predicts poor survival and promotes migration and proliferation of gastric cancer via keeping intracellular alkaline
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RhCG 高表达预示着胃癌生存率较低，并通过保持细胞内碱性来促进胃癌的迁移和增殖。
DOI：
10.1016/j.yexcr.2019.111740
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发表时间：
2020-01-15
影响因子：
3.7
通讯作者：
Huang, JianFei
中科院分区：
文献类型：
--
作者：
Chen, Pei;Liu, Can;Huang, JianFei
晚期胃癌（GC）侵袭性强，死亡率高。恒河猴家族C糖蛋白（RhCG）参与许多癌症的肿瘤进展，但其在胃癌中的功能尚不清楚。结果显示，与正常组织相比，GC组织中RhCG mRNA （P = 0.036）和蛋白水平均过表达（P < 0.05）。RhCG水平高与分化差（P = 0.037）、TNM分期（P < 0.001）、HER-2水平高（P = 0.018）、预后差（P < 0.001）相关。Cox比例风险模型显示，RhCG水平是一个独立的预后生物标志物。RhCG敲低显著降低pH(i)，抑制肿瘤细胞增殖、迁移和侵袭，抑制GC细胞中β -catenin和c-myc的表达。此外，高RhCG水平的GC细胞降低了奥沙利铂的疗效，提示RhCG作为GC的治疗靶点的作用。我们的研究结果揭示了RhCG在胃癌发生、侵袭和转移中的作用。我们认为RhCG可作为一种新的预测胃腺癌预后的指标和治疗靶点。
Advanced gastric cancer (GC) is aggressive with a high mortality rate. Rhesus family, C glycoprotein (RhCG) participates in tumor progression in many cancers, however its function in GC is still unknown. Here, we showed that RhCG was overexpressed in GC tissues at mRNA (P = 0.036) and protein levels (P < 0.05) compared with normal tissues. High RhCG level was correlated with poor differentiation (P = 0.037), TNM stage (P < 0.001), high HER-2 level (P = 0.018) and worse prognosis (P < 0.001). Cox proportional hazard model indicated that RhCG level was an independent prognostic biomarker. RhCG knockdown significantly decreased pH(i) and impeded tumor cellular proliferation, migration and invasion and repressed beta-catenin and c-myc expression in GC cells. Moreover, GC cells with high RhCG level had reduced oxaliplatin efficacy suggesting a role for RhCG as a therapeutic target for GC. Our findings revealed a function of RhCG in cancer pathogenesis, invasion and metastasis in human GC. We suggest that RhCG act may as a novel prognostic indicator and a therapeutic target for gastric adenocarcinoma.