缺氧诱导因子1α和CD133预测直肠癌患者新辅助放化疗疗效的临床研究  

Hypoxia-inducible factor-1α and CD133 predicts pathological complete response and survival for locally advanced rectal cancer patients after neoadjuvant chemoradiotherapy

作　　者：蔡成[1] 王建平[1] 钟志凤[1] 戴志慧[1] 王庆华[1] 董武真 施红旗[2] 刘庆伟[2] 杜金林[1] 

机构地区：[1]浙江省金华市中心医院结直肠肛门外科,浙江金华321099 [2]浙江省金华市中心医院病理科,浙江金华321099

出　　处：《浙江大学学报（医学版）》2017年第1期36-43,共8页Journal of Zhejiang University(Medical Sciences)

基　　金：浙江省金华市社会发展类重点项目(2014-3-010)

摘　　要：目的:评估缺氧诱导因子1α(1IIF-1α)和CD133在接受新辅助放化疗的直肠癌患者病理缓解及预后中的意义。方法:选取2010年1月至2015年12月浙江省金华市中心医院收治的114例病理学检查结果证实为直肠癌的患者,获取放疗前后肿瘤组织标本,RT-PCR检测放化疗前后肿瘤组织HIF-1α和CD133mRNA表达,免疫组织化学方法检测放疗后肿瘤组织HIF-1α和CD133蛋白的表达。Spearman秩相关方法分析HIF-1α与CD133 mRNA表达相关性,单因素及多因素方法分析与直肠癌患者病理学缓解相关的因素,Logistic和Cox回归方法分析与患者总存活率及无病存活率相关的临床病理因素。结果:HIF-1α和CD133mRNA的表达与临床T分期、新辅助放化疗后TNM分期、病理学完全缓解、复发及转移相关,与性别、年龄、体质指数等其他临床因素无关。新辅助放化疗后,HIF-1α与CD133 mRNA表达呈显著正相关(α=0.579,P=0.000)。免疫组织化学检测显示,CD133高表达肿瘤细胞中HIF-1α也呈高表达。单因素分析发现,HIF-1α mRNA(P=0.001)和CD133mRNA表达(P=0.022)与病理学完全缓解相关;多因素分析发现,HIF-1α mRNA(P=0.012)和CD133 mRNA(P=0.047)表达是患者病理学完全缓解的独立预测因子。Cox多因素回归分析发现,HIF-1α mRNA表达(P=0.025)与CD133 mRNA表达(P=0.033)是患者无复发存活的独立预测因子,HIF-1α mRNA表达是患者总存活的独立预测因子(P=0.046)。结论:HIF-1α和CD133与接受新辅助放化疗的直肠癌患者病理学完全缓解及存活显著相关,对两者的研究可能在新辅助放化疗患者的选择及改善患者预后方面具有意义。Objective： To investigate the expression of hypoxia-inducible factor 1α （HIF-1α） and CD133 in predicting pathologic remission and survival of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy. Methods： One hundred and fourteen patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy from January 2010 to December 2015 in Jinhua Municipal Central Hospital were enrolled in the study. RT-PCR and immunohistochemistry methods were used to detect the mRNA and protein expression of HIF-1α and CD133 before and after chemoradiotherapy. Spearman rank correlation was used to analyze the correlation between HIF-1α and CD133 mRNA expression. Univariate and logistic multivariate analyses were used to determine the factors related to pathological complete response （pCR）. Logistic regression analysis and Cox＇ s proportional hazard model were used to determine factors related to overall survival and recurrence-free survival. Results： The expression of HIF-1α and CD133 mRNA was correlated with pT, ypTNM, pCR, recurrence and metastasis of rectal cancer, while not correlated with sex, age and BMI of patients. HIF-1α mRNA expression was positively correlated with CD133 mRNA expression （ α = 0. 579, P = 0. 000 ）. Immunohistochemistry analysis showed that residual cancer cells strongly expressing HIF-1α also expressed CD133 strongly. Univariate analysis showed that HIF-1α mRNA and CD133 mRNA were significantly correlated with pCR （ P = 0. 001, P = 0. 022, respectively ）. Multivariate analysis showed that HIF-1α and CD133 mRNA expression were independent prognostic factors of pCR （P = 0. 012, P = 0. 047, respectively）. Cox regression analysis showed that the expression of HIF-lo~ mRNA and CD133 mRNA were independent predictors of recurrence-free survival and overall survival （ P = 0. 025, P = 0. 033, respectively）. Conclusion： The study indicates that HIF-1α and CD133 can predict pathological complete remission and survival of pa

关 键 词：直肠肿瘤/药物疗法 直肠肿瘤/放射疗法 直肠肿瘤/病理学 缺氧 诱导因子1α亚基/代谢 抗原 CD/代谢 存活率 预后 免疫组织化学 

分 类 号：R735.37[医药卫生—肿瘤]