HIF-1α表达对膀胱尿路上皮癌预后的影响  

Effects of hypoxia-inducible factor-1αexpression on prognosis of human bladder urothelial carcinoma

作　　者：邓光程[1] 张新明[2] 黄智超[3] 王荫槐[3] 赵洪青 吴洪涛[3] DENG Guangcheng;ZHANG Xinming;HUANG Zhichao;WANG Yinhuai;ZHAO Hongqing;WU Hongtao(Department of Urology,Fourth Hospital of Changsha,Changsha,410006,China;Department of Urology,Shenzhen Shekou People’s Hospital;Department of Urology,Second Xiangya Hospital of Central South University)

机构地区：[1]长沙市第四医院泌尿外科,长沙410006 [2]深圳市蛇口人民医院泌尿外科 [3]中南大学湘雅二医院泌尿外科

出　　处：《临床泌尿外科杂志》2020年第8期624-630,634,共8页Journal of Clinical Urology

基　　金：湖南省科学技术厅科技计划项目(No:2013SK3047)。

摘　　要：目的:探讨缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)在膀胱尿路上皮癌(bladder urothelial carcinoma,BUC)中的表达及其与膀胱尿路上皮癌预后的影响。方法:回顾性分析90例手术治疗的膀胱尿路上皮癌患者的临床病理资料,采用免疫组化的方法检测切除标本中HIF-1α的表达情况,Kaplan-Meier法对HIF-1α的表达,血红蛋白含量及吸烟史等变量进行分析,建立Cox比例风险回归模型分析多变量的影响。结果:90例研究对象年龄51~88岁,平均(68.2±9.4)岁,血红蛋白含量75~145 g/L,平均(109.5±13.9)g/L。所有患者均随访5年,中位总生存期为34.0个月,中位无病生存期14.5个月。不同水平HIF-1α表达组之间临床病理分期、组织学分级、吸烟史和血红蛋白水平比较差异有统计学意义(P<0.05)。HIF-1α的表达水平与临床病理分期及组织学分级均正相关(P<0.001)。HIF-1α的表达水平越高,其总生存期(overall survival,OS)及无病生存期(disease-free survival,DFS)越短,差异有统计学意义(P<0.05)。Cox比例风险回归模型中,HIF-1α的表达水平是影响OS及DFS的独立因素(P<0.05),血红蛋白水平是影响DFS的独立因素(P<0.05)。结论:HIF-1α的表达水平是膀胱尿路上皮癌的独立预后因素,且与膀胱尿路上皮癌的预后呈负相关。Objective:To investigate the correlations between hypoxia-inducible factor-1α(HIF-1α)expression,resulting from chronic tumor hypoxia,and the prognosis in patients with bladder urothelial carcinoma(BUC).Method:We retrospectively evaluated the clinicopathological variables of 90 BUC cases who underwent operation.HIF-1αprotein expression and location in the specimens were analyzed by immunohistochemical method.The relationship to clinicopathological variables,including HIF-1αexpression level,serum hemoglobin level,and smoking history were evaluated by the Kaplan-Meier method.A multivariate analysis was performed,according to the Cox proportional hazards regression model.Result:Patient’s age and serum hemoglobin level were 51 to 88 years(mean,68.2±9.4 years)and 75 to 145 g/L(mean,109.5±13.9 g/L),respectively.All patients were followed up for 5 years.The median overall survival(OS)and median disease-free survival(DFS)were 34.0 and 14.5 months,respectively.HIF-1αexpression had significant difference among several clinicopathological variables such as tumor stage,histological grade,smoking history,and serum hemoglobin level(P<0.05).HIF-1αexpression was positively correlated with tumor stage and histological grade(P<0.001).Kaplan-Meier analysis found that high level expression of HIF-1αwas tightly correlated with shorter OS and DFS(P<0.05).Multivariate analyses demonstrated that HIF-1αexpression was an independent prognostic variable for OS(P<0.05)and DFS(P<0.001).In addition,the serum hemoglobin level was an independent prognostic variable for DFS(P<0.05).Conclusion:HIF-1αexpression is an independent prognostic variable for BUC,and its high expression predicts poor prognosis.

关 键 词：膀胱尿路上皮癌 慢性缺氧 缺氧诱导因子1Α 预后 

分 类 号：R737.14[医药卫生—肿瘤]