膀胱尿路上皮癌IDO和Bin1表达临床意义研究

Expression and clinical significance of IDO,Bin1 in bladder urothelial carcinoma tissues

目的探讨膀胱尿路上皮癌组织吲哚胺2,3一二氧化酶（indoleamine 2,3-dioxygenase,IDO）和Bin1蛋白（bridging intergrator protein-1,Bin1）表达及意义。方法收集2007-01-12-2011-07-31昆明医科大学第三附属医院手术切除后石蜡标本84例和同期新鲜标本50例,同期远离癌组织的非肿瘤性膀胱组织为正常膀胱组织共22例,所有新鲜标本采用实时荧光定量PCR检测IDO表达,石蜡标本采用SP法进行免疫组化染色检测IDO和Bin1的表达,并分析其与临床病理特征的相关性。结果膀胱尿路上皮癌组织中IDO阳性表达率为57.14%,Bin1阳性表达率为46.43%。IDO在浸润型膀胱尿路上皮癌组织中表达率明显高于非浸润型,χ2=5.600,P=0.018;随着膀胱尿路上皮癌组织分级（χ2=20.268,P〈0.001）及TNM分期（χ2=12.075,P=0.007）增高,IDO阳性表达率增高;Bin1在浸润型膀胱尿路上皮癌组织中表达明显低于非浸润型（χ2=7.685,P=0.007）,随着膀胱尿路上皮癌组织分级（χ2=15.817,P〈0.001）及TNM分期（χ2=11.104,P=0.010）增高,Bin1阳性表达率降低,差异有统计学意义。膀胱尿路上皮癌组织中IDO表达强度与Bin1表达强度呈负相关（r=-0.306,P=0.003）,与组织学分类（r=0.258,P=0.018）、组织分级（r=0.491,P〈0.001）及TNM分期（r=0.365,P=0.001）呈正相关。Bin1表达强度与组织学分类（r=-0.302,P=0.005）、组织分级（r=-0.411,P〈0.001）及TNM分期（r=-0.302,P=0.005）呈负相关。实时荧光定量PCR检测结果显示,IDO mRNA在膀胱尿路上皮癌组织中的平均表达水平为7.696 1±1.745 28,明显高于正常膀胱组织的6.397 0±1.205 17,t=2.367,P=0.023;Ta和T1期IDO mRNA在膀胱尿路上皮癌组织中的平均表达水平为6.803 4±1.567 53,明显低于T2~T4期的9.183 8±0.690 32,t=4.955,P〈0.001;IDO mRNA在Ⅰ、Ⅱ和Ⅲ级膀胱尿路上皮癌组织中的平均表达水平分别为7.058 7±1.771 57、7.9342±1.530 57和9.290 7±0.574 59,差异有统计学意义,F=4.675,P=0.017。结论 IDO高表达和Bin1低表达或表达缺失与膀胱尿路上皮癌病变进展及预后不良相关,提示IDO和Bin1可能成为膀胱尿路上皮癌患者的预后因子及治疗靶点。

OBJECTIVE To investigate the expression and significance of IDO,Binl in bladder urothelial carcinoma. METHODS Fifty cases fresh specimens,84 cases of paraffin specimens and 22 cases of normal bladder tissue were col lected in the Third Affiliated Hospital of Kunming Medical University from January 12,2007 to July 31,2011. The expres- sions of IDO in fresh specimens were detected by fluorescence quantitative PCR＇. The expressions of IDO and Binl in par- affin specimen were detected by SP method of immunohistoehemical staining and their relationships with clinical pathologi cal characteristics were analyzed. RESULTS The positive expression rate of IDO was 57.14% in bladder urothelial carci- noma,the positive expression rate of Binl was 46.43%. Expression of IDO in invasive bladder urothelial carcinoma was significantly higher than that of no-invasive type （X2 = 5. 600, P = 0. 018）, and the histological grade and TNM stage in- creased with the increasing of positive expression rate of IDO （X2 = 20. 268, P〈0. 001 ; X2 = 12.075, P = 0. 007） ; Bin1 ex- pression in invasive bladder urothelial carcinoma was significantly lower than that of the no-infiltrating type（X2 = 7. 685, P= 0. 007）, the histological grade and TNM stage increased with the decreasing of positive expression rates of Binl （X2 = 15. 817,P〈0. 001;;（2= 11. 104, P= 0. 010）, the difference hadstatistical significance. Correlation analysis showed that,in bladder urothelial carcinoma tissue IDO expression was negatively correlated with Binl expression （r=- 0. 306, P = 0. 003） and positively correlated with the histological classification, histological grade and TNM stage（r= 0. 258, P = 0. 018;r= 0. 491, P〈0. 001 r=0. 365, P= 0. 001）. The expressions of Bin1 were negatively correlated with the histologi- cal classification, histological grade and TNM stage（ r= - 0. 302, P = 0. 005 r= 0. 411, P〈0. 001 ; r= - 0. 302, P = 0. 005）. IDO mRNA average expression in bladder urothelial carcinoma was 7. 696 1±1. 745 28, significantly higher than the average level in normal bladder tissues （6. 397 0 ± 1. 205 17） t= 2. 367, P= 0. 023 IDO mRNA average expression lev- el in Ta,T1 stages was 6. 803 ± 1. 567 53, significantly lower than that in T2 --T4 stages （9. 183 8±0. 690 32）,t= 4. 955, P〈0. 001 The average expression level of IDO mRNA in grade Ⅰ , Ⅱ and Ⅲ of bladder urothelial carcinoma were 7. 058 7±1. 771 57,7. 934 2±1. 530 57 and 9. 290 7±0. 574 59 respectively. The difference was statistically significant, F=4. 675,P=0. 017. CONCLUSION The high expression of IDO and low expression or in expression deletion of Bin1 were associated with bladder urothelial carcinoma progression, IDO, and Binl may be prognostic factors and therapeutic targets for bladder cancer patients.