外周血循环肿瘤细胞的表型及TOP2A表达与膀胱癌复发转移及预后的关系

Relationship between the classification of circulating tumor cells,the expression of TOP2A and the recurrence,metastasis,prognosis of bladder cancer

目的探讨膀胱癌患者外周血循环肿瘤细胞(CTC)的计数、分型及拓扑异构酶Ⅱα(TOP2A)基因表达在膀胱癌复发转移和预后评估中的临床应用价值。方法纳入病理确诊为膀胱癌的患者45例,其中非肌层浸润性膀胱癌(NMIBC)17例,肌层浸润性膀胱癌(MIBC)28例。采用CanPatrolTM二代多重RNA原位检测CTC计数、上皮间质转化(EMT)表型(上皮型、间质型、混合型)及TOP2A的表达量。电话随访患者的生存情况。结果45例患者中有35例(77.8%)检出CTC,共检出CTC 160个,每个样本CTC检出范围0~17个,平均3.56个,中位数3个,其中上皮型40个(25.0%)、间质型53个(33.1%)、混合型67个(41.9%),TOP2A高/中表达的CTC 108个(67.5%)。在间质型CTC中检测到TOP2A高/中表达频率更高(P<0.05)。NMIBC和MIBC两组患者外周血CTC的阳性率、个数、TOP2A高/中表达、TOP2A高/中表达上皮型和TOP2A高/中表达间质型比较,差异有统计学意义(P<0.05)。MIBC患者CTC的检出及其TOP2A高/中表达与无病生存期和总生存期(OS)密切相关(P<0.05);而在单个CTC水平上TOP2A高/中表达与间质型共表达的MIBC患者OS更短(P<0.05)。结论膀胱癌患者CTC中EMT表型与TOP2A表达量存在着不同的表达模式,而CTC中TOP2A表达量越高且间质型与其共同表达,则提示膀胱癌患者临床分期及病理分级越晚,预后越差。

Objective To detect the expression of TOP2A gene and the count,typing of circulating tumor cells(CTCs)in peripheral blood of patients with bladder cancer,and to study their clinical value in metastasis and prognosis of bladder cancer.Methods Forty-five patients with bladder cancer were diagnosed by pathology,including 17 cases of non-muscular invasive bladder cancer(NMIBC)and 28 cases of muscular invasive bladder cancer(MIBC).CTCs count,EMT phenotype and TOP2A quantity were detected by CanPatrolTM second generation multiplex RNA in situ technique.Results The CTCs were detected in 35 of 45 patients(77.8%).A total of 160 CTCs were detected,ranging from 0 to 17,with an average of 3.56 and a median of 3,including 40(25.0%)of epithelial type,53(33.1%)of interstitial type,67(41.9%)of mixed type and 108(67.5%)of CTCs with high/medium expression of TOP2A.Higher frequency of high/medium expression of TOP2A was detected in interstitial cells(P<0.05).There was significant difference in the positive rate and number of CTCs,the high/medium expression of TOP2A,the epithelial type of TOP2A high/medium expression and the interstitial type of high/medium expression of TOP2A between the two groups of NMIBC and MIBC.The detection of CTCs and the high/medium expression of TOP2A on CTCs in patients with MIBC were closely related to disease-free survival and overall survival(OS);while it was found that OS was shorter in patients with MIBC with high/medium expression of TOP2A and interstitial type on CTCs.Conclusions There are different expression patterns between EMT phenotype and TOP2A expression in CTCs,and the higher expression of TOP2A in CTCs and the co-expression of interstitial type and TOP2A suggest the late clinical stage and pathological grade of this kind of bladder cancer and the poor prognosis.