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Quantitative metabolomics and lipoprotein analysis of PDAC patients suggests serum marker categories for pancreatic function, pancreatectomy, cancer metabolism, and systemic disturbances

Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose in the early stages and lacks reliable biomarkers. The scope of this project was to establish quantitative nuclear magnetic resonance (NMR) spectroscopy to comprehensively study blood serum alterations in PDAC patients. Serum samples f...

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Main Authors: Bae, Gyuntae (Author) , Berezhnoy, Georgy (Author) , Flores, Alejandra (Author) , Cannet, Claire (Author) , Schäfer, Hartmut (Author) , Dahlke, Marc-Hendrik (Author) , Michl, Patrick (Author) , Löffler, Markus W. (Author) , Königsrainer, Alfred (Author) , Trautwein, Christoph (Author)
Format: Article (Journal)
Language:English
Published: April 5, 2024
In: Journal of proteome research
Year: 2024, Volume: 23, Issue: 4, Pages: 1249-1262
ISSN:1535-3907
DOI:10.1021/acs.jproteome.3c00611
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1021/acs.jproteome.3c00611
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Author Notes:Gyuntae Bae, Georgy Berezhnoy, Alejandra Flores, Claire Cannet, Hartmut Schäfer, Marc H. Dahlke, Patrick Michl, Markus W. Löffler, Alfred Königsrainer, and Christoph Trautwein
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Summary:Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose in the early stages and lacks reliable biomarkers. The scope of this project was to establish quantitative nuclear magnetic resonance (NMR) spectroscopy to comprehensively study blood serum alterations in PDAC patients. Serum samples from 34 PDAC patients obtained before and after pancreatectomy as well as 83 age- and sex-matched control samples from healthy donors were analyzed with in vitro diagnostics research (IVDr) proton NMR spectroscopy at 600 MHz. Uni- and multivariate statistics were applied to identify significant biofluid alterations. We identified 29 significantly changed metabolites and 98 lipoproteins when comparing serum from healthy controls with those of PDAC patients. The most prominent features were assigned to (i) markers of pancreatic function (e.g., glucose and blood triglycerides), (ii) markers related to surgery (e.g., ketone bodies and blood cholesterols), (iii) PDAC-associated markers (e.g., amino acids and creatine), and (iv) markers for systemic disturbances in PDAC (e.g., gut metabolites DMG, TMAO, DMSO2, and liver lipoproteins). Quantitative serum NMR spectroscopy is suited as a diagnostic tool to investigate PDAC. Remarkably, 2-hydroxybutyrate (2-HB) as a previously suggested marker for insulin resistance was found in extraordinarily high levels only after pancreatectomy, suggesting this metabolite is the strongest marker for pancreatic loss of function.
Item Description:Gesehen am 15.01.2025
Online veröfftentlicht: 26. Februar 2024
Physical Description:Online Resource
ISSN:1535-3907
DOI:10.1021/acs.jproteome.3c00611

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