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.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Pancreatic Ductal/diagnosis , Metabolome , Pancreatic Neoplasms/diagnosis , Phospholipids/blood , Adult , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/blood , Carcinoma, Pancreatic Ductal/pathology , Case-Control Studies , Chromatography, Liquid/methods , Early Diagnosis , Female , Humans , Male , Mass Spectrometry/methods , Metabolomics/methods , Middle Aged , Multivariate Analysis , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/pathology , Principal Component AnalysisABSTRACT
Type 2 diabetes mellitus (T2DM) patients have an increased risk of cardiovascular disease (CVD) that represents one of the main causes of mortality in this population. The knowledge of the underlie factors involved in the development of CVD and the discovery of new biomarkers of the disease could help to early identification of high-risk patients. Using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) we analyzed the serum metabolomic profile of 30 subject distributed according three groups: (i) T2DM patients with CVD; (ii) T2DM patients without CVD; (iii) non-diabetic subjects as controls (C) in order to identify potential biomarkers of the CVD related to T2DM. A partial least squares discriminant analysis (PLS-DA) and one-way analysis of variance (ANOVA) were applied to identify differential metabolites between different groups. Four glycerophospholipids were further identiï¬ed as potential biomarkers of CVD in T2DM patients. Specifically, a reduction in phosphatidylcholine, lysophosphatidylcholine and lysophosphatidylethanolamine (LPE) serum levels were found in T2DM patients compared to controls, presenting the patients with CVD the lowest serum levels of these metabolites. These results show a generalized reduction of circulating phospholipids species in T2DM patients which is more pronounced in those with CVD providing information of the pathways involved in the pathogenesis and progression of CVD associated to T2DM.
