吲哚胺2,3-双加氧酶、c-myc在膀胱尿路上皮癌中的表达及其意义

Expression of IDO and c-myc in bladder urothelial carcinoma and their significance

目的 探讨吲哚胺2,3-双加氧酶（IDO）、c-myc在膀胱尿路上皮癌中的表达及其临床意义.方法 采用荧光定量聚合酶链反应（PCR）检测新鲜肿瘤及黏膜标本各20例IDO mRNA表达,采用SP法检测肿瘤石蜡标本84例及黏膜22例IDO、c-myc蛋白的表达,分析二者与临床病理特征的关系.结果 在膀胱尿路上皮癌组织中,IDO、c-myc蛋白表达强度与患者年龄、性别无关.在浸润型膀胱尿路上皮癌组织中IDO蛋白表达高于非浸润型（x2=5.600,P=0.018）,随着组织分级及国际抗癌联盟（UICC）分期增高,IDO蛋白阳性表达率增高（x2=20.268,P=0.000;x2=12.075,P=0.007）.c-myc蛋白在正常膀胱组织中无阳性表达,在膀胱尿路上皮癌组织中44例（52.4％）表达阳性,二者阳性表达率差异有统计学意义（x2=10.733,P=0.001）;c-myc蛋白表达强度与组织学分类、组织分级及UICC分期无关.在膀胱尿路上皮癌组织中IDO蛋白表达强度与c-myc蛋白表达强度呈正相关（r=0.205,P=0.047）,与组织学分类、组织分级及UICC分期呈正相关（r=0.258,P=0.018;r=0.491,P=0.000;r=0.365,P=0.001）.IDO mRNA在膀胱尿路上皮癌组织中的表达（7.696 1±1.745 2）明显高于正常膀胱组织（6.397 0±1.205 1）（t=2.367,P=0.023）.Ta～T1期膀胱尿路上皮癌组织中IDO mRNA的平均表达水平为6.803 4±1.567 5,明显低于T2～T4期的9.183 8±0.690 3（t=4.955,P=0.000）;IDO mRNA在Ⅰ、Ⅱ、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 5、7.934 2±1.530 5、9.290 7±0.574 5,随着分级增高而增高,差异有统计学意义（t=2.729,P=0.011）.结论 IDO表达与膀胱尿路上皮癌预后不良相关,c-myc表达强度与膀胱尿路上皮癌病变进展无关,但可能与膀胱尿路上皮癌病变发生有关.IDO可能成为膀胱尿路上皮癌预后的预测因子,IDO、c-myc有可能成为肿瘤化疗的一个分子靶向目标.

Objective To investigate the expression and significance of IDO and c-myc in bladder urothelial carcinoma.Methods IDO mRNA expression from fresh tumor and mucosa specimens from 20 cases were detected by fluorescence quantitative PCR,and SP was used to detect the IDO,c-myc protein in paraffin-embeded specimens from 84 cases and mucosa specimens from 22 cases.Results In bladder urothelial carcinoma,IDO,c-myc protein expression level had no relationship with age and sex.Expression of IDO protein in invasive bladder urothelial carcinoma was significantly higher than that of no-invasive （x2 =5.600,P =0.018）.With the increase of the histological grade （x2 =20.268,P =0.000） and UICC stage （x2 =12.075,P =0.007）,the positive expression rate of IDO protein was increased.There was not positive expression of c-myc protein in normal bladder tissue,but in bladder urothelial carcinoma,44 cases （52.4 %） were positive expression （x2 =10.733,P =0.001）.The expression of c-myc protein had no relationship with the histological classification,histological grade and UICC stage.In bladder urothelial carcinoma tissue,IDO protein expression level was positively correlated with c-myc protein expression （r =0.205,P =0.047）,and was positively correlated with the histological classification,histological grade and UICC stage （r =0.258,P =0.018; r =0.491,P =0.000; r =0.365,P =0.001）.Expression of IDO mRNA in bladder urothelial carcinoma （7.696 1±1.745 2） was significantly higher than that in normal bladder tissue （6.397 0±1.205 1）（t =2.367,P =0.023）.The average expression level of IDO mRNA in bladder urothelial carcinoma of Ta-T1 stage was 6.803 4±1.567 5,which was significantly lower than that in T2-T4 stage （9.183 8±0.690 3） （t =4.955,P =0.000）.The average expression levels of IDO mRNA in grade Ⅰ,Ⅱ,Ⅲ bladder urothelial carcinoma were 7.058 7±1.771 5,7.934 2±1.530 5,9.290 7±0.574 5,respectively,which were increased with the grade increasing （t =2.729,P =0.011）.Conclusions The high expression of IDO correlates with bladder urothelial carcinoma progression,and expression of c-myc is irrelevant with bladder urothelial carcinoma progression,but maybe associate with bladder urothelial carcinoma occurrence.IDO may be a predictive factor of prognosis.IDO and c-myc may be therapeutic target in the treatment of bladder urothelial cancer.