Abstract

BACKGROUND:

AQP proteins show a variety of functions in human cell metabolism. The role of different AQP subtypes in tumor metabolism and prognosis are subject of ongoing research.

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.

中文翻译：

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水通道蛋白 (AQP) 3、4、7 和 9 的 mRNA 表达在 pT1 期非肌层浸润性膀胱癌中的预后作用

 抽象的

 背景：

AQP 蛋白在人体细胞代谢中表现出多种功能。不同 AQP 亚型在肿瘤代谢和预后中的作用是正在进行的研究的主题。

 客观的：

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 mRNA 表达及其在治疗决策中的预后价值。

 方法：

对 112 名初次诊断为 pT1 期 NMIBC 的患者进行经尿道膀胱切除术 (TURB) 的福尔马林固定石蜡包埋 (FFPE) 组织以及临床数据和治疗方法进行回顾性分析。使用 RT-qPCR 测量和定量 AQP3、4、7 和 9 的 mRNA 表达。

 结果：

在 112 名患者（83.9% 男性，中位年龄 72 岁）中，40 名患者复发（35.7%），16 名患者进展（14.3%），14 名患者（12.5%）因肿瘤相关死亡。 AQP3 mRNA 表达率为 99.1%，AQP4 为 46.4%，AQP7 为 86.6%，AQP9 为 97.3%。 Spearman 分析揭示了 AQP3、AQP7 和 AQP9 mRNA 表达与不良临床和组织病理学参数（WHO1973 3 级，伴随顺式或多灶性）之间存在统计学显着相关性。 Kaplan-Meier 分析中，AQP9 mRNA 高表达与总队列 ( p = 0.034) 和 3 级肿瘤 ( p = 0.003) 较差的 PFS 相关。在采用膀胱保留方法的患者中，高 AQP3 mRNA 表达与接受 BCG 治疗的患者 CSS 恶化显着相关 ( 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 可能有助于识别可考虑进行早期膀胱切除术的最高风险患者亚组。