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 (1H 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 1H NMR metabolomics to detect bladder cancer (BC) recurrences through a non-invasive approach.
Highlights
Bladder cancer (BC) is the most common cancer of the urinary tract
We present here the results obtained in the frame of a clinical study aiming at the identification of metabolomic signatures for the non-invasive follow-up of non-muscle-invasive bladder cancer (NMIBC) patients and the detection of recurrence according to the changes in the urinary metabolome before and after tumor resection by using 1 H nuclear magnetic resonance (NMR) spectroscopy
We developed a Partial Least Square Discriminant Analysis (PLS-DA) model to discriminate between pre-transurethral resection (TUR) NMIBC (BC) and post-TUR
Summary
Bladder cancer (BC) is the most common cancer of the urinary tract. In men, BC ranks 7th worldwide with over 330,000 new cases per year and it is among the top 10 most deadly cancers [1].At diagnosis, two different entities based on tumor stage are considered: Muscle-invasive bladderCancers 2019, 11, 914; doi:10.3390/cancers11070914 www.mdpi.com/journal/cancersCancers 2019, 11, 914 cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Bladder cancer (BC) is the most common cancer of the urinary tract. BC ranks 7th worldwide with over 330,000 new cases per year and it is among the top 10 most deadly cancers [1]. Two different entities based on tumor stage are considered: Muscle-invasive bladder. Cancers 2019, 11, 914 cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). BC and include tumors with a stage ≥T2. MIBC patients have a bad prognosis (5-year survival
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