Department of Urology and Pediatric Urology, Saarland University, Kirrberger Str 100, 66424, Homburg, Germany.
Department of Ophthalmology, Martin-Luther University Halle-Wittenberg, University Hospital Halle (Saale), Halle (Saale), Germany.
J Cancer Res Clin Oncol. 2019 Nov;145(11):2725-2736. doi: 10.1007/s00432-019-03035-6. Epub 2019 Sep 24.
The identification of biomarkers characterizing the invasive potential of bladder cancer could enhance the clinical management of individual patients and therefore improve prognosis. The aim of this study was to define a miRNA panel in tumor tissues as well as in urinary extracellular vesicles (EVs) for discriminating muscle-invasive bladder cancer (MIBC) from non-muscle-invasive bladder cancer (NMIBC).
miRNA expression was analyzed in 24 formalin-fixed, paraffin-embedded (FFPE) tumor samples by microarray analysis and was further validated by qRT-PCR in 56 FFPE tumor samples as well as in 37 urinary EV samples.
Microarray analysis revealed 63 miRNAs that were significantly differentially expressed (P < 0.05) between tissues from MIBC and NMIBC tumors. Five selected miRNAs (miR-146b-5p, miR-155-5p, miR-138-5p, miR-144-5p, and miR-200a-3p) were validated by qRT-PCR. The expression of all except miR-144-5p was significantly associated with high tumor grade. In urinary EVs, a different expression was verified for miR-146b-5p (P = 0.004) and miR-155-5p (P = 0.036), which exhibited significantly higher expression in urinary EVs from patients with MIBC.
miRNAs are promising biomarkers for the identification of invasive bladder carcinomas. Tissue samples as well as urinary EVs may serve as sources for miRNA analysis. This method, in addition to histopathology, could provide a new diagnostic tool and facilitate individual therapeutic decisions to select patients for early cystectomy.
鉴定能够表征膀胱癌侵袭潜能的生物标志物，可以增强对个体患者的临床管理，从而改善预后。本研究旨在确定肿瘤组织和尿细胞外囊泡（EVs）中的 miRNA 谱，以区分肌层浸润性膀胱癌（MIBC）和非肌层浸润性膀胱癌（NMIBC）。
通过微阵列分析对 24 例福尔马林固定、石蜡包埋（FFPE）肿瘤样本中的 miRNA 表达进行了分析，并在 56 例 FFPE 肿瘤样本和 37 例尿 EV 样本中进一步通过 qRT-PCR 进行了验证。
微阵列分析显示，MIBC 和 NMIBC 肿瘤组织之间有 63 个 miRNA 存在显著差异表达（P<0.05）。通过 qRT-PCR 验证了 5 个选定的 miRNA（miR-146b-5p、miR-155-5p、miR-138-5p、miR-144-5p 和 miR-200a-3p）。除了 miR-144-5p 之外，所有 miRNA 的表达均与高肿瘤分级显著相关。在尿 EVs 中，miR-146b-5p（P=0.004）和 miR-155-5p（P=0.036）的表达存在差异，MIBC 患者的尿 EVs 中这两种 miRNA 的表达明显更高。
miRNAs 是鉴定侵袭性膀胱癌的有前途的生物标志物。组织样本和尿 EVs 都可以作为 miRNA 分析的来源。这种方法除了组织病理学之外，还可以提供一种新的诊断工具，并有助于根据个体治疗决策选择患者进行早期膀胱切除术。
