FOXM1和GRP78在进展期胃癌组织中的表达及其临床意义

目的探讨进展期胃癌组织中叉头框M1（FOXM1）及葡萄糖调节蛋白78（GRP78）的表达及其临床意义。 方法对2010年1月至2015年6月在南通市肿瘤医院行胃癌根治术的168例标本，采用免疫组织化学方法检测进展期胃癌组织及癌旁组织中FOXM1及GRP78的表达情况；应用χ²检验分析进展期胃癌病理特征与FOXM1及GRP78表达的相关性，并应用Cox单因素及多因素分析进展期胃癌预后危险因素。 结果进展期胃癌组织中FOXM1和GRP78的表达率分别为53.57%（90/168）和67.26%（113/168），癌旁组织中二者无表达或弱阳性表达。二者表达在胃癌组织中呈正相关（r=0.41，P<0.001）。FOXM1蛋白表达与脉管癌栓（P<0.001）、淋巴结转移（P<0.001）、T分期（P=0.022）、TNM分期（P<0.001）及分化程度（P<0.001）相关，GRP78蛋白表达与脉管癌栓（P=0.003）、淋巴结转移（P=0.002）及分化程度（P<0.001）相关。FOXM1及GRP78共表达阳性患者术后总生存期显著低于共阴性者，差异具有统计学意义（χ²=35.1189，P<0.001）。FOXM1、T分期是影响进展期胃癌预后的独立危险因素。 结论FOXM1及GRP78可能协同参与了胃癌的发生、发展，并可能成为进展期胃癌临床治疗的新靶点。

Clinical significance of expression of FOXM1 and GRP78 proteins in advanced gastric cancer

ObjectiveTo investigate the expression of forkhead box M1 (FOXM1) and glucose-regulated protein 78 (GRP78) in advanced gastric cancer and to analyze their clinical value. MethodsImmunohistochemical technique was used to detect the expression of FOXM1 and GRP78 proteins in cancerous and paracancerous tissues from 168 patients with advanced gastric cancer. χ² test was used to analyze the correlation between the pathological features of advanced gastric cancer and the expression of FOXM1 and GRP78. Prognostic risk factors for advanced gastric cancer were analyzed by Cox single- and multiple-factor analyses. ResultsThe positive rates of FOXM1 and GRP78 expression in advanced gastric cancer were 53.57% (90/168) and 67.26% (113/168), respectively. No or weak expression of FOXM1 and GRP78 was found in paracancerous tissues. The expression of FOXM1 was positively related to expression of GRP78 in gastric cancer tissues (r=0.41, P<0.001). The expression of FOXM1 protein was correlated with cancer embolus (P<0.001), lymph node metastasis (P<0.001), T stage (P<0.001), TNM stage (P<0.001), and tumor differentiation (P<0.001). The expression of GRP78 protein was correlated with cancer embolus (P=0.003), lymph node metastasis (P=0.002), and tumor differentiation (P<0.001). The overall survival of patients with positive expression of both FOXM1 and GRP78 was shorter than those with negative expression of both proteins (χ²=35.1189, P<0.001). FOXM1 and T stage were independent prognostic factors for advanced gastric cancer. ConclusionFOXM1 and GRP78 may be involved in the development and progression of gastric cancer, and they might become new targets for clinical therapy for advanced gastric cancer.