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

Autores de IIS La Fe

• Alba Loras Monfort

  Autor

• María Carmen Martínez Bisbal

  Autor

• Guillermo Quintas Soriano

  Autor

• Ramón Martínez Máñez

  Autor

• José Luis Ruiz Cerdá

  Autor

Participantes ajenos a IIS La Fe

• GIL, S.

Grupos

• Unidad Mixta de Investigación en Nanomedicina y Sensores

Abstract

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 ( 1 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 1 H NMR metabolomics to detect bladder cancer (BC) recurrences through a non-invasive approach.

Keywords

• biomarker, bladder cancer, metabolic pathways, metabolite, metabolomics, nuclear magnetic resonance, recurrence prediction