摘要
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 clinicopathogenical value of hypoxia-inducible factor-1α （HIF-1α） ,the multidrug resistance protein P-glycoprotein （P-gp） ,muhidrug resistance proteinl （ MRP1 ） and lung resistance protein （ LRP）, and the role of HIF-1α in multidrug resistance of gastric cancer. Methods The expression of HIF-1α, P-gp, MRP1 and LRP was detected in a tissue microarray containing 168 spots of gastric cancer tissue and 27 spots of normal gastric tissue by immunohistochemistry. Results The positive expression rate of HIF-1α, P-gp, MRP1 and LRP in gastric cancer was 51.8% ,51.8%, 45.8% and 55.4% respectively,which was singnificandy higher than that in normal gastric tissue （P 〈 0. 05 ）. HIF-1α expression was correlated with tumor size （ P 〈 0. 01 ）, depth of invasion （ P 〈 0. 01 ）, histology grade （P 〈 0.05 ）, vessel invasion （P 〈 0.01 ） and lymph node metastasis （P 〈 0.01 ）. The expression of HIF-1α, P-gp, and MRP1 had a significant positive relationship （ P 〈 0.05 ）. Kaplan-Meier analysis revealed a significant impact on survival by HIF-1α,P-gp and MRP1 （P 〈0.05）. COX regression indicated that only depth of invasion ,lymph node metastasis and long distant metastasis were independent factors affecting the prognosis of gastric cancer. Conclusion HIF-1α may be involved in the chemotherapeutic risistance of gastric cancer under hypoxia by upregu/ating the expression of P-gp and MRP1. HIF-1α, P-gp and MRP1 may be potentially useful marker for evaluating prognosis of gastric cancer.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2007年第5期537-539,641,共4页
Chinese Journal of Experimental Surgery
关键词
胃肿瘤
缺氧诱导因子
多药耐药
免疫组织化学
Stomach neoplasms
Hyposia-inducible factor
Multidrug resistance
Immunohistochemistry
