Urinary Metabolic Signatures Detect Recurrences in Non-Muscle Invasive Bladder Cancer

Patients with non-muscle invasive bladder cancer (NMIBC) undergo lifelong monitoring based on repeated cystoscopy and urinary cytology due to the high recurrence rate of this tumor. Nevertheless, these techniques have some drawbacks, namely, low accuracy in detection of low-grade tumors, omission of...

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Main Authors: Alba Loras, M. Carmen Martínez-Bisbal, Guillermo Quintás, Salvador Gil, Ramón Martínez-Máñez, José Luis Ruiz-Cerdá
Format: Article
Language:English
Published: MDPI AG 2019-06-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/11/7/914
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author Alba Loras
M. Carmen Martínez-Bisbal
Guillermo Quintás
Salvador Gil
Ramón Martínez-Máñez
José Luis Ruiz-Cerdá
author_facet Alba Loras
M. Carmen Martínez-Bisbal
Guillermo Quintás
Salvador Gil
Ramón Martínez-Máñez
José Luis Ruiz-Cerdá
author_sort Alba Loras
collection DOAJ
description Patients with non-muscle invasive bladder cancer (NMIBC) undergo lifelong monitoring based on repeated cystoscopy and urinary cytology due to the high recurrence rate of this tumor. Nevertheless, these techniques have some drawbacks, namely, low accuracy in detection of low-grade tumors, omission of pre-neoplastic lesions and carcinomas in situ (CIS), invasiveness, and high costs. This work aims to identify a urinary metabolomic signature of recurrence by proton Nuclear Magnetic Resonance (<sup>1</sup>H NMR) spectroscopy for the follow-up of NMIBC patients. To do this, changes in the urinary metabolome before and after transurethral resection (TUR) of tumors are analyzed and a Partial Least Square Discriminant Analysis (PLS-DA) model is developed. The usefulness of this discriminant model for the detection of tumor recurrences is assessed using a cohort of patients undergoing monitoring. The trajectories of the metabolomic profile in the follow-up period provide a negative predictive value of 92.7% in the sample classification. Pathway analyses show taurine, alanine, aspartate, glutamate, and phenylalanine perturbed metabolism associated with NMIBC. These results highlight the potential of <sup>1</sup>H NMR metabolomics to detect bladder cancer (BC) recurrences through a non-invasive approach.
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spelling doaj.art-a538f95c412f4aba9470c8d6311626022023-09-02T19:46:31ZengMDPI AGCancers2072-66942019-06-0111791410.3390/cancers11070914cancers11070914Urinary Metabolic Signatures Detect Recurrences in Non-Muscle Invasive Bladder CancerAlba Loras0M. Carmen Martínez-Bisbal1Guillermo Quintás2Salvador Gil3Ramón Martínez-Máñez4José Luis Ruiz-Cerdá5Unidad Mixta de Investigación en Nanomedicina y Sensores, Universitat Politècnica de València-Instituto de Investigación Sanitaria La Fe, 46026 Valencia, SpainUnidad Mixta de Investigación en Nanomedicina y Sensores, Universitat Politècnica de València-Instituto de Investigación Sanitaria La Fe, 46026 Valencia, SpainAnalytical Unit, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, SpainInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico, Universitat Politècnica de València, Universitat de València, 46022 Valencia, SpainUnidad Mixta de Investigación en Nanomedicina y Sensores, Universitat Politècnica de València-Instituto de Investigación Sanitaria La Fe, 46026 Valencia, SpainUnidad Mixta de Investigación en Nanomedicina y Sensores, Universitat Politècnica de València-Instituto de Investigación Sanitaria La Fe, 46026 Valencia, SpainPatients with non-muscle invasive bladder cancer (NMIBC) undergo lifelong monitoring based on repeated cystoscopy and urinary cytology due to the high recurrence rate of this tumor. Nevertheless, these techniques have some drawbacks, namely, low accuracy in detection of low-grade tumors, omission of pre-neoplastic lesions and carcinomas in situ (CIS), invasiveness, and high costs. This work aims to identify a urinary metabolomic signature of recurrence by proton Nuclear Magnetic Resonance (<sup>1</sup>H NMR) spectroscopy for the follow-up of NMIBC patients. To do this, changes in the urinary metabolome before and after transurethral resection (TUR) of tumors are analyzed and a Partial Least Square Discriminant Analysis (PLS-DA) model is developed. The usefulness of this discriminant model for the detection of tumor recurrences is assessed using a cohort of patients undergoing monitoring. The trajectories of the metabolomic profile in the follow-up period provide a negative predictive value of 92.7% in the sample classification. Pathway analyses show taurine, alanine, aspartate, glutamate, and phenylalanine perturbed metabolism associated with NMIBC. These results highlight the potential of <sup>1</sup>H NMR metabolomics to detect bladder cancer (BC) recurrences through a non-invasive approach.https://www.mdpi.com/2072-6694/11/7/914bladder cancerrecurrence predictionbiomarkermetabolitemetabolomicsmetabolic pathwaysnuclear magnetic resonance
spellingShingle Alba Loras
M. Carmen Martínez-Bisbal
Guillermo Quintás
Salvador Gil
Ramón Martínez-Máñez
José Luis Ruiz-Cerdá
Urinary Metabolic Signatures Detect Recurrences in Non-Muscle Invasive Bladder Cancer
Cancers
bladder cancer
recurrence prediction
biomarker
metabolite
metabolomics
metabolic pathways
nuclear magnetic resonance
title Urinary Metabolic Signatures Detect Recurrences in Non-Muscle Invasive Bladder Cancer
title_full Urinary Metabolic Signatures Detect Recurrences in Non-Muscle Invasive Bladder Cancer
title_fullStr Urinary Metabolic Signatures Detect Recurrences in Non-Muscle Invasive Bladder Cancer
title_full_unstemmed Urinary Metabolic Signatures Detect Recurrences in Non-Muscle Invasive Bladder Cancer
title_short Urinary Metabolic Signatures Detect Recurrences in Non-Muscle Invasive Bladder Cancer
title_sort urinary metabolic signatures detect recurrences in non muscle invasive bladder cancer
topic bladder cancer
recurrence prediction
biomarker
metabolite
metabolomics
metabolic pathways
nuclear magnetic resonance
url https://www.mdpi.com/2072-6694/11/7/914
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