Effects of hypoxia-inducible factor-1α expression on prognosis of human bladder urothelial carcinoma
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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。Abstract: 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-1α protein expression and location in the specimens were analyzed by immunohistochemical method. The relationship to clinicopathological variables, including HIF-1α expression 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-1α expression had significant difference among several clinicopathological variables such as tumor stage, histological grade, smoking history, and serum hemoglobin level(P<0.05). HIF-1α expression was positively correlated with tumor stage and histological grade(P<0.001). Kaplan-Meier analysis found that high level expression of HIF-1α was tightly correlated with shorter OS and DFS(P<0.05). Multivariate analyses demonstrated that HIF-1α expression 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-1α expression is an independent prognostic variable for BUC, and its high expression predicts poor prognosis.
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Key words:
- bladder urothelial carcinoma /
- chronic hypoxia /
- hypoxia-inducible factor-1α /
- prognosis
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