Characterization of a MiRNA Signature with Enhanced Diagnostic and Prognostic Power for Patients with Bladder Carcinoma

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Nov 25

PMID 38003433

Authors

Maria Samara

Panagiotis J Vlachostergios

Eleni Thodou

Ioannis Zachos

Lampros Mitrakas

Konstantinos Evmorfopoulos

Vassilios Tzortzis

Antonis Giakountis

Affiliations

Soon will be listed here.

Abstract

Bladder carcinoma is globally among the most prevalent cancers and is associated with a high mortality rate at advanced stages. Its detection relies on invasive diagnostic methods that are unpleasant for the patient. Non-invasive molecular biomarkers, such as miRNAs, could serve as alternatives for early detection and prognosis of this malignancy. We designed a computational approach that combines transcriptome profiling, survival analyses, and calculation of diagnostic power in order to isolate miRNA signatures with high diagnostic and prognostic utility. Our analysis of TCGA-BLCA data from 429 patients yielded one miRNA signature, consisting of five upregulated and three downregulated miRNAs with cumulative diagnostic power that outperforms current diagnostic methods. The same miRNAs have a strong prognostic significance since their expression is associated with the overall survival of bladder cancer patients. We evaluated the expression of this signature in 19 solid cancer types, supporting its unique diagnostic utility for bladder carcinoma. We provide computational evidence regarding the functional implications of this miRNA signature in cell cycle regulation, demonstrating its abundance in body fluids, including peripheral blood and urine. Our study characterized a novel miRNA signature with the potential to serve as a non-invasive method for bladder cancer diagnosis and prognosis.

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References

Christofidis K, Moulavasilis N, Fragkiadis E, Goutas D, Lazaris A, Mitropoulos D . Diagnosis of Low-Grade Urothelial Neoplasm in the Era of the Second Edition of the Paris System for Reporting Urinary Cytology. Diagnostics (Basel). 2023; 13(16). PMC: 10453841. DOI: 10.3390/diagnostics13162625. View

Galvao-Lima L, Morais A, Valentim R, Barreto E . miRNAs as biomarkers for early cancer detection and their application in the development of new diagnostic tools. Biomed Eng Online. 2021; 20(1):21. PMC: 7885381. DOI: 10.1186/s12938-021-00857-9. View

Chang L, Zhou G, Soufan O, Xia J . miRNet 2.0: network-based visual analytics for miRNA functional analysis and systems biology. Nucleic Acids Res. 2020; 48(W1):W244-W251. PMC: 7319552. DOI: 10.1093/nar/gkaa467. View

Karakiewicz P, Shariat S, Palapattu G, Perrotte P, Lotan Y, Rogers C . Precystectomy nomogram for prediction of advanced bladder cancer stage. Eur Urol. 2006; 50(6):1254-60. DOI: 10.1016/j.eururo.2006.06.010. View

Blanca A, Sanchez-Gonzalez A, Requena M, Carrasco-Valiente J, Gomez-Gomez E, Cheng L . Expression of miR-100 and miR-138 as prognostic biomarkers in non-muscle-invasive bladder cancer. APMIS. 2019; 127(8):545-553. DOI: 10.1111/apm.12973. View

Wan P, Chen Z, Huang M, Jiang H, Wu H, Zhong K . miR-200a-3p facilitates bladder cancer cell proliferation by targeting the gene. Transl Androl Urol. 2022; 10(11):4262-4274. PMC: 8661264. DOI: 10.21037/tau-21-941. View

Yossepowitch O, Herr H, Donat S . Use of urinary biomarkers for bladder cancer surveillance: patient perspectives. J Urol. 2007; 177(4):1277-82. DOI: 10.1016/j.juro.2006.11.066. View

Fang L, Du W, Yang W, Rutnam Z, Peng C, Li H . MiR-93 enhances angiogenesis and metastasis by targeting LATS2. Cell Cycle. 2012; 11(23):4352-65. PMC: 3552918. DOI: 10.4161/cc.22670. View

Grimaldi A, Nuzzo S, Condorelli G, Salvatore M, Incoronato M . Prognostic and Clinicopathological Significance of MiR-155 in Breast Cancer: A Systematic Review. Int J Mol Sci. 2020; 21(16). PMC: 7461504. DOI: 10.3390/ijms21165834. View

10.

Schmitz-Drager C, Bonberg N, Pesch B, Todenhofer T, Sahin S, Behrens T . Replacing cystoscopy by urine markers in the follow-up of patients with low-risk non-muscle-invasive bladder cancer?-An International Bladder Cancer Network project. Urol Oncol. 2016; 34(10):452-9. DOI: 10.1016/j.urolonc.2016.06.001. View

11.

Hofbauer S, de Martino M, Lucca I, Haitel A, Susani M, Shariat S . A urinary microRNA (miR) signature for diagnosis of bladder cancer. Urol Oncol. 2018; 36(12):531.e1-531.e8. DOI: 10.1016/j.urolonc.2018.09.006. View

12.

Vila-Navarro E, Fernandez-Castaner E, Rovira-Rigau M, Raimondi G, Vila-Casadesus M, Lozano J . MiR-93 is related to poor prognosis in pancreatic cancer and promotes tumor progression by targeting microtubule dynamics. Oncogenesis. 2020; 9(5):43. PMC: 7198506. DOI: 10.1038/s41389-020-0227-y. View

13.

Rupani H, Sanchez-Elsner T, Howarth P . MicroRNAs and respiratory diseases. Eur Respir J. 2012; 41(3):695-705. DOI: 10.1183/09031936.00212011. View

14.

Han S, Jhun B, Kim S, Moon S, Yang B, Kwon O . miRNA Expression Profiles and Potential as Biomarkers in Nontuberculous Mycobacterial Pulmonary Disease. Sci Rep. 2020; 10(1):3178. PMC: 7035291. DOI: 10.1038/s41598-020-60132-0. View

15.

Singh G, Storey K . MicroRNA Cues from Nature: A Roadmap to Decipher and Combat Challenges in Human Health and Disease?. Cells. 2021; 10(12). PMC: 8699674. DOI: 10.3390/cells10123374. View

16.

McCarthy D, Chen Y, Smyth G . Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res. 2012; 40(10):4288-97. PMC: 3378882. DOI: 10.1093/nar/gks042. View

17.

Witjes J, Morote J, Cornel E, Gakis G, P van Valenberg F, Lozano F . Performance of the Bladder EpiCheck™ Methylation Test for Patients Under Surveillance for Non-muscle-invasive Bladder Cancer: Results of a Multicenter, Prospective, Blinded Clinical Trial. Eur Urol Oncol. 2019; 1(4):307-313. DOI: 10.1016/j.euo.2018.06.011. View

18.

Tribolet L, Kerr E, Cowled C, Bean A, Stewart C, Dearnley M . MicroRNA Biomarkers for Infectious Diseases: From Basic Research to Biosensing. Front Microbiol. 2020; 11:1197. PMC: 7286131. DOI: 10.3389/fmicb.2020.01197. View

19.

Serrano M, Garrido-Navas M, Diaz Mochon J, Cristofanilli M, Gil-Bazo I, Pauwels P . Precision Prevention and Cancer Interception: The New Challenges of Liquid Biopsy. Cancer Discov. 2020; 10(11):1635-1644. DOI: 10.1158/2159-8290.CD-20-0466. View

20.

Ludwig N, Leidinger P, Becker K, Backes C, Fehlmann T, Pallasch C . Distribution of miRNA expression across human tissues. Nucleic Acids Res. 2016; 44(8):3865-77. PMC: 4856985. DOI: 10.1093/nar/gkw116. View