结肠癌组织NRP-1和VEGF表达及其与预后相关性  

Expression of neuropilin-1 and VEGF and its relationship with prognosis in colon cancer

作　　者：王辉[1] 李峰[1] 刘龙飞[1] 易世杰[1] 赵骏 夏红星[1] 彭易 陈明道 谢荣俊[1] WANG Hui;LI Feng;LIU Long-fei;YI Shi-jie;ZHAO Jun;XIA Hong-xing;PENG Yi;CHEN Ming-dao;XIE Rong-jun(Department of Gastrointestinal Surgery,Affiliated Nanhua Hospital,University of South China,Hengyang 421002,P.R.China)

机构地区：[1]南华大学附属南华医院胃肠外科,湖南衡阳421002

出　　处：《中华肿瘤防治杂志》2020年第6期445-450,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：湖南省卫生计生委科研计划(C2017019);衡阳市科技计划(2016KS09)。

摘　　要：目的结肠癌的发生发展过程与肿瘤血管生成密切相关,神经纤毛蛋白-1(neuropilin-1,NRP-1)和血管内皮生长因子(vascular endothelial growth factor,VEGF)在肿瘤血管生成中发挥重要作用。本研究旨在探讨结肠癌组织NRP-1和VEGF表达及其预后的关系。方法收集2010-08-01-2012-05-31南华大学附属南华医院普外胃肠病区手术切除、具有完整资料、术后经病理确诊的结肠癌及癌旁(>5cm)组织标本73例,采用免疫组织化学法检测NRP-1及VEGF在结肠癌及癌旁正常组织的表达;另外选取2016年南华大学附属南华医院切除结肠癌新鲜组织及癌旁组织(距癌组织>5cm)16对,采用蛋白质印迹法检测NRP-1及VEGF表达。结果免疫组化结果显示,与结肠癌癌旁组织比较,结肠癌组织中NRP-1及VEGF呈高表达,χ^2=55.857,P<0.001;χ^2=44.042,P<0.001。蛋白质印迹法检测结果显示,新鲜结肠癌组织中NRP-1及VEGF蛋白呈高表达,而癌旁组织中表达降低,差异有统计学意义,t=-63.238,P<0.001;t=-78.712,P<0.001。结肠癌组织中NRP-1和VEGF高表达均与肿瘤大小、TNM分期、淋巴结有无转移有关联,差异有统计学意义,P<0.05;癌胚抗原(carcinoembryonic antigen,CEA)的数值与NRP-1表达有关联(χ^2=15.966,P=0.002),而与VEGF表达无统计学意义的关联,χ^2=0.061,P=0.862;Cox多因素回归分析显示,CEA(RR=4.851,95%CI:1.013~23.427)、肿瘤大小(RR=0.157,95%CI:0.017~1.228)、TNM分期(RR=5.419,95%CI:2.179~32.479)、淋巴结转移(RR=0.137,95%CI:0.023~0.728)是NRP-1阳性表达的独立影响因素;生存分析显示,NRP-1阳性表达组患者生存周期短于阴性患者,χ^2=5.081,P=0.029。结论NRP-1参与结肠癌的血管生成,并导致预后不良,提示NRP-1在结肠癌发生发展中起重要作用,为评估结肠癌预后及研究靶向药物提供新的思路。OBJECTIVE The occurrence of colon cancer is closely related to tumor angiogenesis when Neuropilin-1(NRP-1)and Vascular Endothelial Growth Factor(VEGF)both play important roles in tumor angiogenesis.Therefore,in order to explore their role in the occurrence and development of colon cancer,as well as its relationship with prognosis,we aim to investigate the expression of NRP-1 and VEGF in colon cancer.METHODS From Aug.1,2010,to May 31,2012,73 pathologically proved cases of colon cancer and paracancerous tissues(>5 cm)with complete data were collected from the gastrointestinal surgery department of Nanhua Hospital affiliated to the University of South China which were used to detect the expressions of NRP-1 and VEGF by immunohistochemistry.Sixteen pairs of freshly frozen colon cancer tissues and corresponding paracancerous tissues were used to detect the expression of NRP-1 and VEGF by Western-blot.RESULTS The results of immunohistochemistry showed that the expressions of NRP-1 and VEGF in colon cancer were higher than that in the adjacent tissues of colon cancer(χ^2=55.857,P<0.001;χ^2=44.042,P<0.001).In addition,The results of Western-blot showed that the expressions of NRP-1 and VEGF protein in fresh colon cancer tissues were higher,while the expressions of VEGF protein in paracancerous tissue were lower than that in fresh colon cancer tissue(t=-63.238,P<0.001;t=-78.712,P<0.001).The high expression of NRP-1 and VEGF was closely correlated with tumor size,TNM stage and lymph node metastasis(P<0.05),and the differences among them were statistically significant(P<0.05).The value of CEA was correlated with the expression of NRP-1(χ^2=15.966,P=0.002),but not with the expression of VEGF(χ^2=0.061,P=0.862).COX multiple factors regression analysis showed that the CEA(RR=4.851,95%CI=1.013-23.427),tumor size(RR=0.157,95%CI=0.017-1.228),TNM staging(RR=5.419,95%CI=2.179-32.479),lymph node metastasis(RR=0.137,95%CI=0.023-0.728)were independent factors of positive expression of NRP-1.Survival analysis showed that the surviv

关 键 词：结肠癌 血管生成 预后 神经纤毛蛋白-1 血管内皮生长因子 

分 类 号：R735.3[医药卫生—肿瘤]