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目的探讨缺氧诱导因子(HIF)-1α与耐药蛋白P糖蛋白(P-gp)、多药耐药相关蛋白1(MRP1)、肺耐药相关蛋白(LRP)在胃癌中的表达及HIF-1α在胃癌耐药中的作用。方法通过免疫组织化学方法研究含有168例的胃癌病例和27例正常胃组织的组织芯片中HIF-1α和耐药蛋白P-g、MRP1、LRP的表达及其关系。结果HIF-1α和耐药蛋白P-gp、MRP1、LRP在胃癌中的阳性表达率分别为51.8%、51.8%、45.8%、55.4%,均明显高于在正常胃组织中的表达(P<0.05)。HIF-1α与肿瘤大小、分化程度、浸润深度、脉管浸润、淋巴结转移显著相关。HIF-1α和P-gp,MRP1之间显著正相关(P<0.05)。Kaplan-Meier分析显示HIF-1α和P-gp、MRP1阳性组的预后较阴性组差(P<0.05),COX回归多因素分析显示浸润深度,淋巴结转移和远处转移是独立预后因素。结论缺氧可能通过HIF-1α上调耐药蛋白P-gp、MRP1的表达参与胃癌化疗耐药形成。HIF-1α、P-gp和MRP1可能成为评价胃癌预后和耐药的有价值指标。
Objective To investigate the expression of HIF-1α, P-gp, MRP1 and LRP in gastric carcinoma and the relationship between HIF-1α and P-gp, -1α in Gastric Cancer Drug Resistance. Methods The expression of HIF-1α, P-g, MRP1 and LRP in tissue microarray including 168 cases of gastric cancer and 27 cases of normal gastric tissue were studied by immunohistochemistry. Results The positive rates of HIF-1α and P-gp, MRP1 and LRP in gastric cancer were 51.8%, 51.8%, 45.8% and 55.4%, respectively, which were significantly higher than those in normal gastric tissues (P < 0.05). HIF-1α was significantly associated with tumor size, differentiation, depth of invasion, vascular invasion and lymph node metastasis. There was a significant positive correlation between HIF-1α, P-gp and MRP1 (P <0.05). Kaplan-Meier analysis showed that the prognosis of HIF-1alpha and P-gp, MRP1-positive group was worse than that of negative group (P <0.05). Multivariate analysis of COX regression showed that the depth of invasion, lymph node metastasis and distant metastasis were independent prognostic factors. Conclusion Hypoxia may be involved in the chemoresistance of gastric cancer through the up-regulation of the expression of P-gp and MRP1 by HIF-1α. HIF-1α, P-gp and MRP1 may be valuable indicators for evaluating the prognosis and drug resistance of gastric cancer.