胃癌原发灶中上皮间质转化相关因子和CD133的表达及其与临床病理特征和预后的关系

Epithelial-Mesenchymal Transition Related Factors and CD133 Protein Expressions in Primary Lesion of Gastric Cancer and Its Relationship with Clinicopathologic Features and Prognosis

目的研究上皮间质转化(EMT)相关因子Snail、E-cadherin、N-cadherin与胃癌患者临床病理特征、预后及胃癌肿瘤起始细胞表面标志物CD133表达的关系。方法利用Western blot方法检测50例胃癌及癌旁正常胃黏膜组织中EMT相关因子及CD133蛋白的定位及定量表达,分析EMT相关因子及CD133蛋白表达与胃癌患者的临床病理学指标的关系,Spearman等级相关分析EMT相关因子和CD133表达的关系,Kaplan-Meier方法分析EMT相关因子及CD133表达与胃癌患者生存的关系。结果①胃癌组织中Snail、N-cadherin及CD133蛋白表达相对灰度值明显高于其在癌旁正常胃黏膜组织中的表达(Snail:0.599±0.114比0.259±0.108,P=0.020;N-cadherin:0.754±0.154比0.329±0.134,P=0.001;CD133:0.635±0.119比0.485±0.116,P=0.029),E-cadherin蛋白表达相对灰度值明显低于其在癌旁正常胃黏膜组织中的表达(0.378±0.123比0.752±0.156,P=0.003)。②Snail蛋白、N-cadherin蛋白表达平均相对灰度值在有血管浸润、淋巴管浸润、N3淋巴结转移及肿瘤直径≥5 cm和Ⅲ+Ⅳ期胃癌患者中的表达明显高于无血管浸润、淋巴管浸润、N0～N2淋巴结转移及肿瘤直径<5 cm和Ⅰ+Ⅱ期的胃癌患者(P<0.05),而E-cadherin蛋白表达平均相对灰度值在有血管浸润、淋巴管浸润、N3淋巴结转移及Ⅲ+Ⅳ期胃癌患者中的表达显著低于无血管浸润、淋巴管浸润、N0～N2淋巴结转移及Ⅰ+Ⅱ期的胃癌患者(P<0.05),CD133蛋白表达平均相对灰度值在有淋巴管浸润、N3淋巴结转移、肿瘤直径≥5 cm和Ⅲ+Ⅳ期胃癌患者中的表达显著高于无淋巴管浸润、N0～N2淋巴结转移、肿瘤直径<5 cm和Ⅰ+Ⅱ期的胃癌患者(P<0.05)。③Snail、N-cadherin蛋白表达与CD133蛋白表达分别均呈正相关(rs=0.278,P=0.048;rs=0.406,P=0.003),而E-cadherin蛋白表达与CD133蛋白表达呈负相关(rs=-0.504,P=0.000)。④Snail、N-cadherin及CD133蛋白低表达组的生存时间明显长于其高表达者(P<0.05),联合EMT相关因子和CD133蛋白表达能够最有效预测患者生存。结论EMT与胃癌肿瘤起始细胞特性之间存在明显相关,并且两者与胃癌的高侵袭的临床病理特征相关,联合EMT相关因子Snail、E-cadherin、N-cadherin与CD133能够最有效预测胃癌患者的预后。

Objective To investigate the prognostic value of epithelial-mesenchymal transition（EMT） related proteins（Snail,E-cadherin,and N-cadherin） in gastric cancer and its relationship with tumor initiating cells（TICs） marker（CD133）.Methods The expressions of EMT-related proteins and CD133 protein in the gastric cancer tissues and normal gastric mucosa tissues adjacent to gastric cancer were detected by Western blot method.The relations between the expressions of EMT-related factors proteins and CD133 protein and the clinicopathologic characters were analyzed.The correlations between EMT-related factors and CD133 were analyzed by Spearman.The correlations between EMT-related factors expressions and CD133 expression and survival were analyzed by Kaplan-Meier method and Log-rank test.Results ① The protein expression levels of Snail,N-cadherin,and CD133 in the gastric cancer tissues were significantly higher than those in the normal gastric mucosa tissues adjacent to gastric cancer（Snail：0.599± 0.114 versus 0.259±0.108,P=0.020;N-cadherin：0.754±0.154 versus 0.329±0.134,P=0.001;CD133：0.635± 0.119 versus 0.485±0.116,P=0.029）,while the protein expression level of E-cadherin was lower than that in the normal gastric mucosa tissues adjacent to gastric cancer（0.378±0.123 versus 0.752±0.156,P=0.003）.② The expression levels of Snail and N-cadherin in the gastric cancer patients with vascular invasion,lymphatic vessel invasion,N3 lymph node metastasis,diameter more than 5 cm,and Ⅲ＋Ⅳ staging were significantly higher than those in the patients without vascular invasion,lymphatic vessel invasion,N0-N2 lymph node metastasis,diameter less than 5 cm,andⅠ＋Ⅱ staging（P〈0.05）,while E-cadherin protein expression was lower than that in the patients without vascular invasion,lymphatic vessel invasion,N0？-？N2 lymph nodes metastasis,andⅠ＋Ⅱstaging（P〈0.05）.The expression levels of CD133 in the gastric cancer patients with lymphatic vessel invasion,diameter more than 5 cm,and Ⅲ＋Ⅳ staging were significantly higher than those in the patients without lymphatic vessel invasion,diameter less than 5 cm,andⅠ＋Ⅱ staging（P〈0.05）.③The Snail and N-cadherin protein expressions were significantly positive correlated with CD133 protein expression,respectively（rs？=0.278,P=0.048;rs？=0.406,P=0.003）,while E-cadherin protein expression was significantly negative correlated with CD133 protein expression（rs？=-0.504,P=0.000）.④ The survival time in the patients with lower expressions of Snail,N-cadherin,and CD133 were significantly longer than those in the patients with higher expressions of Snail,N-cadherin,and CD133（P〈0.05）.The combination of Snail,N-cadherin,E-cadherin,and CD133 could effectively predict survival.Conclusions There is a significant correlation between EMT and gastric cancer TICs,and which are correlated with aggressive clinicopathologic features of gastric cancer.The combination of Snail,E-cadherin,N-cadherin,and CD133 may be effectively predict the prognosis of gastric cancer patients.