微小RNA-202和转录因子性别决定区Y框蛋白9在膀胱癌组织中表达与临床病理特征及预后的关系

The relationship between the expression of microRNA-202(miR-202)and transcription factor sex-determining region Y-box protein 9(Sox9)and clinicopathological features and prognosis in bladder cancer

目的探讨微小RNA 202(miR-202)和转录因子性别决定区Y框蛋白9(Sox9)在膀胱癌中的表达及与临床预后的关系。方法选取2012年6月至2013年12月河南大学第一附属医院肿瘤科收治的120例行切除术的膀胱癌病人作为研究对象,收集癌组织(n=120)及癌旁正常组织(n=120),采用免疫组化检测组织中Sox9蛋白表达,采用荧光定量PCR(qRT-PCR)检测癌组织及癌旁组织中miR-202和Sox9表达量,观察两组组织中miR-202、Sox9表达水平、与临床病理参数关系、二者相关性及与病人预后关系。结果膀胱癌组织中Sox9阳性表达率为70.83%,癌旁组织为31.67%,差异有统计学意义(P<0.05);膀胱癌组织中miR-202水平低于癌旁组织(P<0.05),Sox9水平高于癌旁组织(P<0.05);miR-202、Sox9表达与年龄、性别、肌层浸润无关(P>0.05),与病理分级及淋巴结转移相关(P<0.05);膀胱癌组织中miR-202和Sox9表达呈负相关性(r=-0.835,P=0.000);膀胱癌组织中miR-202高表达病人中位生存时间为(48.61±1.82)个月,高于低表达组的(37.99±2.47)个月(P<0.05),miR-202高表达病人预后5年生存率为52.94%,高于低表达组的30.77%(P<0.05);Sox9高表达病人中位生存时间为(39.78±2.60)个月,低于低表达组的(49.62±1.90)个月(P<0.05),Sox9高表达病人预后5年生存率为38.18%,低于低表达组的60.00%(P<0.05);TNM分期、淋巴结转移、Sox9是影响病人预后的独立危险因素,miR-202是影响膀胱癌病人预后的保护因素。结论膀胱癌组织中miR-202低表达,Sox9高表达,二者表达呈正相关,与病人病理分级及淋巴结转移相关,miR-202低表达与Sox9高表达生存期短,预后差,可能作为膀胱癌预后评估的潜在标记物。

Objective To investigate the expressions of microRNA-202(miR-202)and transcription factor sex-determining region Y-box protein 9(Sox9)in bladder cancer and their relationships with clinical prognosis.Methods A total of 120 patients with bladder cancer who underwent resection in Oncology Department of First Affiliated Hospital of Henan University from June 2012 to December 2013 were selected as the study subjects,cancer tissues(n=120)and normal adjacent tissues(n=120)were collected,immunohistochemistry was used to detect the expression of Sox9 protein in tissues,quantitative fluorescence PCR(qRT-PCR)was used to detect the expressions of miR-202 and SOX-9 in cancer tissues and adjacent tissues.The expressions of miR-202 and Sox9 in the tissues,their relationships with clinicopathological parameters,the correlation between them,and their relationships with prognosis of the patients in the two groups were observed.Results The positive expression rate of Sox9 in bladder cancer tissues was 70.83%,and that in adjacent tissues was 31.67%,and the difference was statistically significant(P<0.05);the level of miR-202 in bladder cancer tissues was lower than that in adjacent tissues(P<0.05),and the level of Sox9 was higher than that in adjacent tissues(P<0.05);the expressions of miR-202 and Sox9 were not correlated with age,sex and muscle invasion(P>0.05),but were correlated with pathological grade and lymph node metastasis(P<0.05);there was a negative correlation between the expressions of miR-202 and SOX-9 in bladder cancer(r=-0.835,P=0.000);the median survival time of patients with miR-202 high expression in bladder cancer tissue was(48.61±1.82)months,which was higher than(37.99±2.47)months of patients with low expression(P<0.05),the 5-year survival rate of patients with miR-202 high expression was 52.94%,which was higher than 30.77%of patients with miR-202 low expression(P<0.05);the median survival time of patients with Sox9 high expression was(39.78±2.60)months,which was lower than(49.62±1.90)months of patients with Sox9 low expression(P<0.05),the 5-year survival rate of patients with Sox9 high expression was 38.18%,which was lower than 60.00%of patients with Sox9 low expression(P<0.05);TNM staging,lymph node metastasis,and Sox9 were independent risk factors for the progno sis of patients.miR-202 was a protective factor affecting the prognosis of patients with bladder cancer.Conclusions The expression of miR-202 is low and Sox9 is high in bladder cancer tissues,and they are positively correlated and related to pathological grade and lymph node metastasis.The low expression of miR-202 and high expression of Sox9 correlate with short survival time and poor prognosis,which may be potential markers for prognosis evaluation of bladder cancer.