HIF-1α在胃癌组织中的表达及其临床意义

Expression and Clinical Significance of Hypoxia-inducible Factor-1α in Gastric Cancer

背景与目的:近年来发现缺氧诱导因子-1α(hypoxia-induciblefactor-1α,HIF-1α)与多种恶性肿瘤的发生、发展、转移及预后等多种生物学行为相关。本研究通过免疫组织化学方法检测HIF-1α的表达,探讨HIF-1α在胃癌组织中的表达及其临床意义。方法:对96例患者的胃癌组织学蜡块,应用免疫组织化学SP法检测HIF-1α的表达,并分析HIF-1α的表达与患者临床病理特征及预后的关系。结果:96例患者中,80.2%(77/96)的患者HIF-1α呈阳性表达,其中(+)7例,(++)29例,(+++)27例,(++++)14例;Ⅰ、Ⅱ期与Ⅲ、Ⅳ期患者的HIF-1α表达率分别为66.7%、87.3%(P=0.016),T1、T2浸润深度与T3、T4浸润深度的患者HIF-1α表达率分别为57.9%、88.0%(P=0.007),无远处转移与有远处转移患者的HIF-1α表达率分别为75.9%、100.0%(P=0.055)。HIF-1α阳性表达患者的生存率低于阴性表达者;阳性表达与阴性表达的患者5年生存率分别为31.2%及57.9%(P=0.027)。经Cox多因素回归分析,HIF-1α尚不能做为胃癌的独立预后因素(P=0.158)。结论:HIF-1α的阳性表达与胃癌患者的总生存率、肿瘤分期、浸润深度及远处转移关系密切;提示HIF-1α可作为评估胃癌发展、转移及预后的参考指标之一。

BACKGROUND ＆ OBJECTIVE： Hypoxia-inducible factor-1α （HIF-1α） is correlated to the genesis, progression, invasion, metastasis, and prognosis of some malignancies. This study was to evaluate the expression of HIF-1α in gastric cancer, and explore its correlation to clinical features of gastric cancer. METHODS： The expression of HIF-1α in 96 specimens of gastric cancer was detected by SP immunohistochemistry. The correlations of HIF-1α to clinicopathologic features and prognosis of gastric cancer were analyzed with SPSS10.0 software. RESULTS： Of the 96 specimens, 77 （80.2%） were HIF-1α-positive： 7 were grade （＋）, 29 were grade （＋＋）, 27 were grade （＋＋＋）, and 14 were grade （＋＋＋＋）. The positive rate of HIF-1α was significantly lower in stage Ⅰ - Ⅱ patients than in stage Ⅲ-Ⅳ patients （66.7% vs. 87.3%, P=0.016）, significantly lower in stage T1-T2 patients than in stage T3-T4 patients （57.9% vs. 88.0%, P= 0.007）, and slightly lower in the patients without distant metastasis than in the patients with distant metastasis （75.9% vs. 100%, P=0.055）. The 5-year overall survival rate was significantly lower in HIF-1α-positive patients than in HIF-1α-negative patients （31.2% vs. 57.9%, P=0.027）. However, HIF-1α was not an independent prognostic factor of gastric cancer in multivariate analysis. CONCLUSIONS： The expression of HIF-1α is correlated to patients＇ survival, tumor stage, invasion depth, and distant metastasis of gastric cancer, and may be considered as a reference criterion in evaluating the progression, metastasis, and prognosis of gastric cancer.