title: Untargeted LC-HRMS-Based Metabolomics for Searching New Biomarkers of Pancreatic Ductal Adenocarcinoma: A Pilot Study.
abstract: Pancreatic ductal adenocarcinoma is one of the most lethal tumors since it is usually detected at an advanced stage in which surgery and/or current chemotherapy have limited efficacy. The lack of sensitive and specific markers for diagnosis leads to a dismal prognosis. The purpose of this study is to identify metabolites in serum of pancreatic ductal adenocarcinoma patients that could be used as diagnostic biomarkers of this pathology. We used liquid chromatography-high-resolution mass spectrometry for a nontargeted metabolomics approach with serum samples from 28 individuals, including 16 patients with pancreatic ductal adenocarcinoma and 12 healthy controls. Multivariate statistical analysis, which included principal component analysis and partial least squares, revealed clear separation between the patient and control groups analyzed by liquid chromatography-high-resolution mass spectrometry using a nontargeted metabolomics approach. The metabolic analysis showed significantly lower levels of phospholipids in the serum from patients with pancreatic ductal adenocarcinoma compared with serum from controls. Our results suggest that the liquid chromatography-high-resolution mass spectrometry-based metabolomics approach provides a potent and promising tool for the diagnosis of pancreatic ductal adenocarcinoma patients using the specific metabolites identified as novel biomarkers that could be used for an earlier detection and treatment of these patients.
authors.affiliation: 1 Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Granada, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ríos Peces
authors.affiliation: 1 Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Granada, Spain.
authors.forename: Caridad
authors.initials: C
authors.lastname: Díaz Navarro
authors.affiliation: 2 Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Márquez López
authors.affiliation: 3 Department of Health Science, University of Jaen, Jaen, Spain.|4 Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain.
authors.forename: Octavio
authors.initials: O
authors.lastname: Caba
authors.affiliation: 4 Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain.|5 Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Jiménez-Luna
authors.affiliation: 4 Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain.|6 Biosanitary Institute of Granada (ibs. GRANADA), SAS-Universidad de Granada, Granada, Spain.
authors.forename: Consolación
authors.initials: C
authors.lastname: Melguizo
authors.affiliation: 4 Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain.|6 Biosanitary Institute of Granada (ibs. GRANADA), SAS-Universidad de Granada, Granada, Spain.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Prados
authors.affiliation: 1 Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Granada, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Genilloud
authors.affiliation: 1 Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Granada, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Vicente Pérez
authors.affiliation: 1 Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Granada, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Pérez Del Palacio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D010743:Phospholipids / Q000097:blood*; D025341:Principal Component Analysis
chemical_list: D014408:Biomarkers, Tumor; D010743:Phospholipids
keywords: biomarker; diagnosis; hydrophilic interaction liquid chromatography (HILIC); liquid chromatography–high-resolution mass spectrometry (LC-HRMS); pancreatic ductal adenocarcinoma (PDAC); reverse-phase liquid chromatography (RPLC)