大肠癌组织中PIK3CA、PIK3CB蛋白与多药耐药基因产物表达的相关性及其临床意义  

Expression of PIK3CA, PIK3CB and proteins associated with multidrug resistance in colorectal carcinoma

作　　者：温菲菲 吴淑华[1] 李扬扬[1] 高向前[1] 何双[1] 

机构地区：[1]滨州医学院附属医院病理科,山东省滨州市256603

出　　处：《世界华人消化杂志》2015年第2期202-209,共8页World Chinese Journal of Digestology

基　　金：山东省科技攻关基金资助项目;No.2010GSF10259~~

摘　　要：目的:检测PIK3CA、PIK3CB和多药耐药基因1(muhidrug resistance 1,MDR-1)、肺耐药蛋白(lung cancer resistance protein,LRP)、谷胱甘肽转移酶π(glutathione-S-transferaseπ,GST-π)、D N A拓扑异构酶Ⅱ(DNA topoisomeraseⅡ,TopoⅡ)在大肠癌中的表达,探讨PIK3CA、PIK3CB对大肠癌多药耐药性的影响.方法:应用免疫组织化学EnVision法检测316例大肠癌组织中PIK3CA、PIK3CB、MDR-1、LRP、GST-π和TopoⅡ的表达情况,并结合临床病理因素进行分析.结果:316例大肠癌中,PIK3CA、PIK3CB的表达与肿瘤的分化程度、淋巴结转移成正相关,其相关系数分别为0.136、0.168.MDR基因在大肠癌组织中的阳性率分别为:M D R-1为72.78%(230/316)、L R P为70.89%(224/316)、TOPⅡ为77.53%(245/316)及GST-π为76.58%(242/316).经Spearman相关性分析,PIK3CA、PIK3CB的表达与多药耐药蛋白MDR-1、LRP、GST-π的表达均成正相关,相关系数分别为0.288、0.128、0.1 9 7.3 1 6例大肠癌患者的中位生存期为60 mo,5年生存率为47.5%,Kaplan-Meier分析结果显示,PIK3CA与PIK3CB同时高表达、淋巴结转移、MDR-1(+)、GST-π(+)患者术后5年生存率明显降低.Cox比例风险模型显示,PIK3CA(+)PIK3CB(+)、淋巴结转移、MDR-1、GST-π是影响大肠癌患者预后的独立因素.结论:PIK3CA、PIK3CB与大肠癌的多药耐药密切相关,PIK3CA、PIK3CB、淋巴结转移、MDR-1、GST-π是影响大肠癌患者预后的独立因素,检测PIK3CA、PIK3CB为临床合理选择化疗药物、初步判断预后具有重要参考价值.AIM： To investigate the clinical significance of expression of PIK3 CA, PIK3 CB and proteins associated with multidrug resistance（MDR） in colorectal cancer（CRC） and to analyze their correlations.METHODS： Immunohistochemistry was employed to detect the expression of PIK3 CA, PIK3 CB, multidrug resistance-1（MDR-1）, lung cancer resistance protein（ L R P）, glutathione- S-transferase π（GST-π）, and DNA topoisomerase Ⅱ（Topo Ⅱ） in 316 CRC specimens. Patientswere followed annually by telephone or at an outpatient clinic. RESULTS： The overexpression rates of MDR-1, LRP, Topo II, and GST-π in CRC were found to be 72.78%, 70.89%, 77.53%, and 76.58%, respectively. Correlation analysis showed that PIK3 CA and PIK3 CB expression exhibited a positive correlation with MDR-1, LRP, and GST-π expression（r = 0.288, 0.128, and 0.197, respectively; P 〈0.05）. PIK3 CA and PIK3 CB expression was correlated with the degree of tumor differentiation and lymph node metastasis（P〈 0.05）. Kaplan-Meier analysis revealed that the 5-year survival rate was significantly correlated with lymph node metastasis, positive expression of PIK3 CA and PIK3 CB, and negative expression of GST-π and MDR-1. Multivariate analysis revealed that GST-π and MDR-1 expression and lymph node metastasis could serve as independent predictive factors of overall survival. CONCLUSION： The expression of both PIK3 CA and PIK3 CB is increased and related to the development and progression of CRC and MDR. The combined detection of PIK3 CA and PIK3 CB is of great significance for prognostic evaluation and therapy optimization in patients with CRC.

关 键 词：大肠癌 多药耐药基因 PIK3CA PIK3CB 预后 

分 类 号：R735.34[医药卫生—肿瘤]