OBJECTIVE: To investigate the mRNA expression of Aquaporin (AQP) 3, 4, 7 and 9 in pT1 non-muscle-invasive bladder cancer (NMIBC) and its prognostic value in therapeutic decision making.
METHODS: Formalin-fixed-paraffin-embedded (FFPE) tissues from transurethral resection of the bladder (TURB) from 112 patients with initial diagnosis of stage pT1 NMIBC were analyzed retrospectively together with clinical data and therapeutic approaches. mRNA expression of AQP3, 4, 7 and 9 was measured and quantified using RT-qPCR.
RESULTS: Of the 112 patients (83.9%male, median age 72 years), 40 had a recurrence (35.7%), 16 a progression (14.3%) and 14 patients (12.5%) died tumor-related. mRNA expression for AQP3 was detected in 99.1%, AQP4 in 46.4%, AQP7 in 86.6%and AQP9 in 97.3%. Spearman analysis revealed statistically significant correlations between AQP3, AQP7 and AQP9 mRNA expression with adverse clinical and histopathological parameters (WHO1973 grade 3, concomitant Cis or multifocality). High AQP9 mRNA expression was associated with worse PFS in the total cohort (p = 0.034) and in Grade 3 tumors (p = 0.003) in Kaplan-Meier analysis. In patients with bladder sparing approach, high AQP3 mRNA expression was significantly associated with worse CSS in patients receiving BCG therapy (p = 0.029).
CONCLUSIONS: mRNA expression of AQP3, 7 and 9 correlates with adverse clinical and pathological parameters. AQP3 and 9 may help to identify a subgroup of highest risk patients who may be considered for early cystectomy.
目的:探讨水通道蛋白(AQP)3、4、7和9在pT1非肌层浸润性膀胱癌(NMIBC)中的表达及其在治疗决策中的预后价值。
方法:回顾性分析112例经尿道膀胱电切术(TURB)的福尔马林固定石蜡包埋(FFPE)组织的临床资料和治疗方法。使用RT-qPCR测量和定量AQP3、4、7和9的mRNA表达。
结果:在112例患者中(83.9%为男性,中位年龄72岁),40例复发(35.7%),16个进展(14.3%)和14个患者(12.5%)死亡与肿瘤相关。AQP3的mRNA表达量为99.1%,AQP4占46.4%,AQP7占86.6%,AQP9占97.3%。Spearman分析显示,AQP3,AQP7和AQP9mRNA表达与不良临床和组织病理学参数(WHO19733级,伴随的顺式或多灶性)之间存在统计学上的显着相关性。在Kaplan-Meier分析中,高AQP9mRNA表达与总队列(p=0.034)和3级肿瘤(p=0.003)中PFS较差相关。在保留膀胱方法的患者中,在接受BCG治疗的患者中,高AQP3mRNA表达与CSS恶化显著相关(p=0.029).
结论:AQP3、7和9的mRNA表达与不良临床和病理参数相关。AQP3和9可能有助于确定可能考虑早期膀胱切除术的高危患者亚组。