Untargeted LC-HRMS-Based Metabolomics for Searching New Biomarkers of Pancreatic Ductal Adenocarcinoma: A Pilot Study

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.

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Discovery of Pancreatic Adenocarcinoma Biomarkers by Untargeted Metabolomics

Cancers ◽

10.3390/cancers12041002 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1002 ◽

Cited By ~ 2

Author(s):

Ariadna Martín-Blázquez ◽

Cristina Jiménez-Luna ◽

Caridad Díaz ◽

Joaquina Martínez-Galán ◽

Jose Prados ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

High Resolution ◽

High Resolution Mass Spectrometry ◽

Untargeted Metabolomics ◽

Ductal Adenocarcinoma ◽

Serum Samples ◽

High Resolution Mass ◽

Negative Electrospray Ionization ◽

Resolution Mass

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers, with a 5-year survival rate of less than 5%. In fact, complete surgical resection remains the only curative treatment. However, fewer than 20% of patients are candidates for surgery at the time of presentation. Hence, there is a critical need to identify diagnostic biomarkers with potential clinical utility in this pathology. In this context, metabolomics could be a powerful tool to search for new robust biomarkers. Comparative metabolomic profiling was performed in serum samples from 59 unresectable PDAC patients and 60 healthy controls. Samples were analyzed by using an untargeted metabolomics workflow based on liquid chromatography, coupled to high-resolution mass spectrometry in positive and negative electrospray ionization modes. Univariate and multivariate analysis allowed the identification of potential candidates that were significantly altered in PDAC patients. A panel of nine candidates yielded excellent diagnostic capacities. Pathway analysis revealed four altered pathways in our patients. This study shows the potential of liquid chromatography coupled to high-resolution mass spectrometry as a diagnostic tool for PDAC. Furthermore, it identified novel robust biomarkers with excellent diagnostic capacities.

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