Liquid Biopsy Biomarkers in Urine: A Route Towards Molecular Diagnosis and Personalized Medicine of Bladder Cancer

Overview

Journal J Pers Med

Date 2021 Apr 3

PMID 33806972

Citations 51

Authors

Matteo Ferro

Evelina La Civita

Antonietta Liotti

Michele Cennamo

Fabiana Tortora

Carlo Buonerba

Felice Crocetto

Giuseppe Lucarelli

Gian Maria Busetto

Francesco Del Giudice

Ottavio de Cobelli

Giuseppe Carrieri

Angelo Porreca

Amelia Cimmino

Daniela Terracciano

Affiliations

Soon will be listed here.

Abstract

Bladder cancer (BC) is characterized by high incidence and recurrence rates together with genomic instability and elevated mutation degree. Currently, cystoscopy combined with cytology is routinely used for diagnosis, prognosis and disease surveillance. Such an approach is often associated with several side effects, discomfort for the patient and high economic burden. Thus, there is an essential demand of non-invasive, sensitive, fast and inexpensive biomarkers for clinical management of BC patients. In this context, liquid biopsy represents a very promising tool that has been widely investigated over the last decade. Liquid biopsy will likely be at the basis of patient selection for precision medicine, both in terms of treatment choice and real-time monitoring of therapeutic effects. Several different urinary biomarkers have been proposed for liquid biopsy in BC, including DNA methylation and mutations, protein-based assays, non-coding RNAs and mRNA signatures. In this review, we summarized the state of the art on different available tests concerning their potential clinical applications for BC detection, prognosis, surveillance and response to therapy.

Citing Articles

Mechanistic insights into PROS1 inhibition of bladder cancer progression and angiogenesis via the AKT/GSK3β/β-catenin pathway.

Fan X, Wang J, Chen S, Li X, Cao J, Wang H Sci Rep. 2025; 15(1):4748.

PMID: 39922934 PMC: 11807197. DOI: 10.1038/s41598-025-89217-4.

Microsatellite Instability in Urine: Breakthrough Method for Bladder Cancer Identification.

Rico-Mendez M, Ayala-Madrigal M, Gonzalez-Mercado A, Gutierrez-Angulo M, Ramirez de Arellano Sanchez J, Beltran-Ontiveros S Biomedicines. 2025; 12(12.

PMID: 39767633 PMC: 11727160. DOI: 10.3390/biomedicines12122726.

Diagnosis of early-stage bladder cancer via unprocessed urine samples at the point of care.

Keum C, Yeom H, Noh T, Yi S, Jin S, Kim C Nat Biomed Eng. 2024; .

PMID: 39609560 DOI: 10.1038/s41551-024-01298-0.

A Preliminary Analysis of Circulating Tumor Microemboli from Breast Cancer Patients during Follow-Up Visits.

Lai H, Huang H, Hao Y, Lee H, Wang C, Ling T Curr Oncol. 2024; 31(9):5677-5693.

PMID: 39330049 PMC: 11431662. DOI: 10.3390/curroncol31090421.

Contemporary Molecular Markers for Predicting Systemic Treatment Response in Urothelial Bladder Cancer: A Narrative Review.

Dimitrov G, Mangaldzhiev R, Slavov C, Popov E Cancers (Basel). 2024; 16(17).

PMID: 39272913 PMC: 11394076. DOI: 10.3390/cancers16173056.

References

Laguna T, Wagner B, Starcher B, Luckey Tarro H, Mann S, Sagel S . Urinary desmosine: a biomarker of structural lung injury during CF pulmonary exacerbation. Pediatr Pulmonol. 2012; 47(9):856-63. PMC: 3856884. DOI: 10.1002/ppul.22525. View

Breen V, Kasabov N, Kamat A, Jacobson E, Suttie J, OSullivan P . A holistic comparative analysis of diagnostic tests for urothelial carcinoma: a study of Cxbladder Detect, UroVysion® FISH, NMP22® and cytology based on imputation of multiple datasets. BMC Med Res Methodol. 2015; 15:45. PMC: 4494166. DOI: 10.1186/s12874-015-0036-8. View

Goodison S, Ogawa O, Matsui Y, Kobayashi T, Miyake M, Ohnishi S . A multiplex urinary immunoassay for bladder cancer detection: analysis of a Japanese cohort. J Transl Med. 2016; 14(1):287. PMC: 5055716. DOI: 10.1186/s12967-016-1043-1. View

DAndrea D, Soria F, Zehetmayer S, Gust K, Korn S, Witjes J . Diagnostic accuracy, clinical utility and influence on decision-making of a methylation urine biomarker test in the surveillance of non-muscle-invasive bladder cancer. BJU Int. 2019; 123(6):959-967. PMC: 6850401. DOI: 10.1111/bju.14673. View

Hosen M, Sheikh M, Zvereva M, Scelo G, Forey N, Durand G . Urinary TERT promoter mutations are detectable up to 10 years prior to clinical diagnosis of bladder cancer: Evidence from the Golestan Cohort Study. EBioMedicine. 2020; 53:102643. PMC: 7118568. DOI: 10.1016/j.ebiom.2020.102643. View

Trenti E, Pycha S, Mian C, Schwienbacher C, Hanspeter E, Kafka M . Comparison of 2 new real-time polymerase chain reaction-based urinary markers in the follow-up of patients with non-muscle-invasive bladder cancer. Cancer Cytopathol. 2020; 128(5):341-347. DOI: 10.1002/cncy.22246. View

Hurle R, Lazzeri M, Vanni E, Lughezzani G, Buffi N, Casale P . Active Surveillance for Low Risk Nonmuscle Invasive Bladder Cancer: A Confirmatory and Resource Consumption Study from the BIAS Project. J Urol. 2017; 199(2):401-406. DOI: 10.1016/j.juro.2017.08.091. View

van Kessel K, Van Neste L, Lurkin I, Zwarthoff E, Van Criekinge W . Evaluation of an Epigenetic Profile for the Detection of Bladder Cancer in Patients with Hematuria. J Urol. 2015; 195(3):601-7. DOI: 10.1016/j.juro.2015.08.085. View

Babjuk M, Bohle A, Burger M, Capoun O, Cohen D, Comperat E . EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol. 2016; 71(3):447-461. DOI: 10.1016/j.eururo.2016.05.041. View

10.

Anastasi E, Maggi M, Tartaglione S, Angeloni A, Gennarini G, Leoncini P . Predictive value of MCM5 (ADXBLADDER) analysis in urine of men evaluated for the initial diagnosis of bladder cancer: A comparative prospective study. Diagn Cytopathol. 2020; 48(11):1034-1040. DOI: 10.1002/dc.24530. View

11.

Olivieri M, Ferro M, Terreri S, Durso M, Romanelli A, Avitabile C . Long non-coding RNA containing ultraconserved genomic region 8 promotes bladder cancer tumorigenesis. Oncotarget. 2016; 7(15):20636-54. PMC: 4991481. DOI: 10.18632/oncotarget.7833. View

12.

Soria F, Droller M, Lotan Y, Gontero P, DAndrea D, Gust K . An up-to-date catalog of available urinary biomarkers for the surveillance of non-muscle invasive bladder cancer. World J Urol. 2018; 36(12):1981-1995. PMC: 6280823. DOI: 10.1007/s00345-018-2380-x. View

13.

D Elia C, Pycha A, Folchini D, Mian C, Hanspeter E, Schwienbacher C . Diagnostic predictive value of Xpert Bladder Cancer Monitor in the follow-up of patients affected by non-muscle invasive bladder cancer. J Clin Pathol. 2018; 72(2):140-144. DOI: 10.1136/jclinpath-2018-205393. View

14.

Terracciano D, Ferro M, Terreri S, Lucarelli G, DElia C, Musi G . Urinary long noncoding RNAs in nonmuscle-invasive bladder cancer: new architects in cancer prognostic biomarkers. Transl Res. 2017; 184:108-117. DOI: 10.1016/j.trsl.2017.03.005. View

15.

Bryzgunova O, Skvortsova T, Kolesnikova E, Starikov A, Rykova E, Vlassov V . Isolation and comparative study of cell-free nucleic acids from human urine. Ann N Y Acad Sci. 2006; 1075:334-40. DOI: 10.1196/annals.1368.045. View

16.

Hayashi Y, Fujita K, Matsuzaki K, Eich M, Tomiyama E, Matsushita M . Clinical Significance of Hotspot Mutation Analysis of Urinary Cell-Free DNA in Urothelial Bladder Cancer. Front Oncol. 2020; 10:755. PMC: 7250242. DOI: 10.3389/fonc.2020.00755. 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.

Roupret M, Gontero P, McCracken S, Dudderidge T, Stockley J, Kennedy A . Diagnostic Accuracy of MCM5 for the Detection of Recurrence in Nonmuscle Invasive Bladder Cancer Followup: A Blinded, Prospective Cohort, Multicenter European Study. J Urol. 2020; 204(4):685-690. DOI: 10.1097/JU.0000000000001084. View

19.

Murtaza M, Dawson S, Tsui D, Gale D, Forshew T, Piskorz A . Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013; 497(7447):108-12. DOI: 10.1038/nature12065. View

20.

Hanke M, Hoefig K, Merz H, Feller A, Kausch I, Jocham D . A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol Oncol. 2009; 28(6):655-61. DOI: 10.1016/j.urolonc.2009.01.027. View