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Open AccessArticle

Prognostic Stratification of Bladder Cancer Patients with a MicroRNA-Based Approach

Veneto Institute of Oncology IOV—IRCCS, 35128 Padua, Italy
Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy
Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy
Authors to whom correspondence should be addressed.
These authors contributed equally.
Cancers 2020, 12(11), 3133;
Received: 1 October 2020 / Revised: 20 October 2020 / Accepted: 21 October 2020 / Published: 26 October 2020
(This article belongs to the Collection Regulatory and Non-Coding RNAs in Cancer Epigenetic Mechanisms)
The majority of patients with bladder cancer are diagnosed before the malignant cells invade the bladder’s muscle wall, and can be treated with surgery. These patients are nevertheless at high risk of disease recurrence and progression to muscle-invasive disease, and must undergo periodic cystoscopy and urine cytology, procedures that are burdensome for the patient and for the healthcare system. We set out to identify a follow-up/risk assessment test that analyzes the levels of a specific class of RNA molecules (microRNAs) in urine samples. Results led to the discovery of a panel of microRNAs in urine samples that identifies high-risk bladder cancer patients with high accuracy and predicts event-free survival. This urine microRNA assay thus holds promise as a noninvasive alternative to current methods for bladder cancer follow-up.
Robust non-invasive tests for prognostic stratification of bladder cancer (BCa) patients are in high demand. Following a comprehensive analysis of studies on BCa, we selected a panel of 29 microRNAs (miRNAs) and analyzed their levels in urine and plasma samples in a prospective cohort of 63 BCa patients (32 at high risk of recurrence and 31 low-risk cases) and 37 healthy controls using RT-qPCR. To design an assay suitable for large-scale testing, we applied a hierarchical pipeline to select the miRNAs that were not affected by confounding factors such as haematuria and urine specific gravity, and exceeded stringent cut-off criteria (fold change > 2.5 and p-value < 0.005). Using a two-step decision tree based on the urine levels of miR-34a-5p, miR-200a-3p and miR-193a-5p, normalized against miR-125b-5p, patients could be classified as high- or low-risk with a sensitivity of 0.844, specificity of 0.806 and accuracy of 0.825. Furthermore, univariate Cox proportional hazards regression analyses indicated that increased urine levels of miR-29a-3p, miR-34a-5p, miR-193a-5p, miR-200c-3p, miR-205-5p and miR-532-5p were associated with a shorter event-free survival (hazard ratios > 3.1, p-value < 0.05). Taken together, our findings suggest that measuring the urine levels of these miRNAs could provide a novel cost-effective, noninvasive test for risk assessment of BCa patients. View Full-Text
Keywords: microRNAs; liquid biopsy; bladder cancer; prognostic stratification microRNAs; liquid biopsy; bladder cancer; prognostic stratification
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MDPI and ACS Style

Cavallari, I.; Grassi, A.; Del Bianco, P.; Aceti, A.; Zaborra, C.; Sharova, E.; Bertazzolo, I.; D’Agostino, D.M.; Iafrate, M.; Ciminale, V. Prognostic Stratification of Bladder Cancer Patients with a MicroRNA-Based Approach. Cancers 2020, 12, 3133.

AMA Style

Cavallari I, Grassi A, Del Bianco P, Aceti A, Zaborra C, Sharova E, Bertazzolo I, D’Agostino DM, Iafrate M, Ciminale V. Prognostic Stratification of Bladder Cancer Patients with a MicroRNA-Based Approach. Cancers. 2020; 12(11):3133.

Chicago/Turabian Style

Cavallari, Ilaria; Grassi, Angela; Del Bianco, Paola; Aceti, Alberto; Zaborra, Carlotta; Sharova, Evgeniya; Bertazzolo, Irene; D’Agostino, Donna M.; Iafrate, Massimo; Ciminale, Vincenzo. 2020. "Prognostic Stratification of Bladder Cancer Patients with a MicroRNA-Based Approach" Cancers 12, no. 11: 3133.

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