Untargeted metabolomics of prostate cancer zwitterionic and positively charged compounds in urine

Prostate cancer, a leading cause of cancer-related deaths worldwide, principally occurs in over 50-year-old men. Nowadays there is urgency to discover biomarkers alternative to prostate-specific antigen, as it cannot discriminate patients with benign prostatic hyperplasia from clinically significant...

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Detalles Bibliográficos
Autores: Cerrato, Andrea, Bedia, Carmen, Capriotti, Anna Laura, Cavaliere, Chiara, Gentile, Vincenzo, Maggi, Martina, Montone, Carmela Maria, Piovesana, Susy, Sciarra, Alessandro, Tauler, Romà, Laganà, Aldo
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/237373
Acceso en línea:http://hdl.handle.net/10261/237373
Access Level:acceso abierto
Palabra clave:Untargeted metabolomics
Positively charged compounds
Polar compounds
Chemometrics
ROI-MCR-ALS
LC-HRMS
Descripción
Sumario:Prostate cancer, a leading cause of cancer-related deaths worldwide, principally occurs in over 50-year-old men. Nowadays there is urgency to discover biomarkers alternative to prostate-specific antigen, as it cannot discriminate patients with benign prostatic hyperplasia from clinically significant forms of prostatic cancer. In the present paper, 32 benign prostatic hyperplasia and 41 prostatic cancer urine samples were collected and analyzed. Polar and positively charged metabolites were therein investigated using an analytical platform comprising an up to 40-fold analyte enrichment step by graphitized carbon black solid-phase extraction, HILIC separation, and untargeted high-resolution mass spectrometry analysis. These classes of compounds are often neglected in common metabolomics experiments even though previous studies reported their significance in cancer biomarker discovery. The complex metabolomics big datasets, generated by the UHPLC-HRMS, were analyzed with the ROIMCR procedure, based on the selection of the MS regions of interest data and their analysis by the Multivariate Curve-Resolution Alternating Least Squares chemometrics method. This approach allowed the resolution and tentative identification of the metabolites differentially expressed by the two data sets. Among these, amino acids and carnitine derivatives were tentatively identified highlighting the importance of the proposed methodology for cancer biomarker research.