β-catenin、Wnt1、Smad4、Hoxa9、Bmi-1与食管鳞癌预后的关系  

Relationship of β-catenin,Wnt1,Smad4,Hoxa9 and Bmi-1 expression with the prognosis of esophageal squamous cell carcinoma

作　　者：吕进[1,2] 曹秀峰[1,2] 纪律[1,2] 朱斌[1,2] 陶磊[1,2] 王冬冬[1,2] 

机构地区：[1]南京医科大学附属南京第一医院肿瘤外科 [2]南京医科大学肿瘤中心,江苏省南京市210006

出　　处：《世界华人消化杂志》2010年第27期2874-2883,共10页World Chinese Journal of Digestology

基　　金：南京市医学发展重点基金资助项目;No.ZKX0114~~

摘　　要：目的:探讨β-catenin、Wnt1、Smad4、Hoxa9、Bmi-1基因与食管鳞癌(esophageal squamous cell carcinoma,ESCC)预后及临床病理的关系.方法:从南京医科大学附属第一医院2002-07/2003-12106例ESCC石蜡标本中随机选取70例.运用免疫组织化学及实时定量PCR检测70例ESCC患者肿瘤切除石蜡标本中待测基因的mRNA及蛋白表达水平,统计学分析其与ESCC预后及临床病理的关系.结果:ESCC中的β-catenin、Wnt1、Smad4、Hoxa9、Bmi-1mRNA表达水平明显高于癌旁组织(0.0821±0.0416vs0.0185±0.0201,P=0.0000;1.9934±1.9888vs0.8863±0.6658,P=0.0184;0.0298±0.0215vs0.0189±0.0187,P=0.0017;2.098±0.091vs1.016±0.078,P=0.0000;2.181±2.158vs0.931±0.894,P=0.0152).ESCC中的β-catenin、Wnt1、Smad4、Hoxa9、Bmi-1的蛋白水平明显高于癌旁组织(0.2835±0.0844vs0.2352±0.0670,P=0.0003;0.3830±0.0947vs0.2721±0.1474,P=0.0000;0.2637±0.0348vs0.2042±0.0180,P=0.0000;0.2058±0.0316vs0.1218±0.0518,P=0.0000;0.2736±0.0834vs0.2251±0.0571,P=0.0001).除Smad4外,待测基因mRNA及蛋白质表达水平均与病理分期和淋巴结转移相关(均P<0.05),高表达者预后较差(均P<0.05),但Hoxa9蛋白质表达水平与预后无关(P>0.05).Smad4mRNA表达水平与病理分期和淋巴结转移相关(均P<0.05),mRNA低水平表达者预后欠佳(均P<0.05);蛋白质表达水平与病理分期有关(P<0.05),但与淋巴结转移无关(P>0.05),与患者预后无关(P>0.05).Logistic多因素分析显示预后有关的因素有β-catenin、Wnt1、Bmi-1表达阳性或Wnt1及β-catenin二者表达阳性者或Wnt1、β-catenin、Bmi-1三者表达阳性者(χ2=17.65,P=0.0072).结论:Wnt1/β-catenin、Bmi-1高表达者预后不佳,表达水平与ESCC临床病理分期、淋巴结转移呈逆相关;Smad4、Hoxa9mRNA表达水平虽与ESCC预后及临床病理分期、淋巴结转移相关,但可能不是独立的预后因素.AIM：To investigate the association of β-catenin,Wnt1,Smad4,Hoxa9 and Bmi-1 expression with the prognosis and clinicopathologic characteristics of patients with esophageal squamous cell carcinoma（ESCC）.METHODS：Seventy paraffin-embedded ESCC specimens collected at Nanjing First Hospital from July 2002 to December 2003 were studied.The mRNA and protein expression of β-catenin,Wnt1,Smad4,Hoxa9 and Bmi-1 in these specimens was detected by real-time quantitative RT-PCR and immunohistochemistry.The correlation between the expression of these markers with the prognosis and clinicopathologic characteristics of ESCC patients was then analyzed.RESULTS：The mRNA expression levels of β-catenin,Wnt1,Smad4,Hoxa9 and Bmi-1 in ESCC were significantly higher than those in tumor-adjacent non-cancerous tissue（0.0821 ± 0.0416 vs 0.0185 ± 0.0201,P = 0.0000;1.9934 ± 1.9888 vs 0.8863 ± 0.665,P = 0.0184;0.0298 ± 0.0215 vs 0.0189 ± 0.0187,P = 0.0017;2.098 ± 0.091 vs 1.016 ± 0.078,P = 0.0000;2.181 ± 2.158 vs 0.931 ± 0.894,P = 0.0152）.The protein expression levels of β-catenin,Wnt1,Smad4,Hoxa9 and Bmi-1 in ESCC were also signifi cantly higher than those in tumor-adjacent non-cancerous tissue（0.2835 ± 0.0844 vs 0.2352 ± 0.0670,P = 0.0003;0.3830 ± 0.0947 vs 0.2721 ± 0.1474,P = 0.0000;0.2637 ± 0.0348 vs 0.2042 ± 0.0180,P = 0.0000;0.2058 ± 0.0316 vs 0.1218 ± 0.0518,P = 0.0000;0.2736 ± 0.0834 vs 0.2251 ± 0.0571,P = 0.0001）.Except for Smad4,the mRNA and protein levels of all the other markers were closely associated with pathological stage and lymph node metastasis in ESCC patients（all P 0.05）.The protein level of Hoxa9 was not associated with the prognosis of ESCC（P 0.05）.The hypo-expression of Smad4 mRNA was closely associated with advanced pathological stage,lymph node metastasis and prognosis in patients with ESCC（all P 0.05）.The Smad4 protein expression level was associated with pathological stage（P 0.05）,but not with prognosis and lymph node metastasis（P 0.05）.Multivariate logisti

关 键 词：食管鳞癌 Β-CATENIN Wnt-1 BMI-1 SMAD4 HOXA9 预后 临床病理 

分 类 号：R735.1[医药卫生—肿瘤]