Quantitative
Metabolomics and Lipoprotein Analysis
of PDAC Patients Suggests Serum Marker Categories for Pancreatic Function,
Pancreatectomy, Cancer Metabolism, and Systemic Disturbances
Version 2 2024-02-27, 19:26Version 2 2024-02-27, 19:26
Version 1 2024-02-26, 14:09Version 1 2024-02-26, 14:09
journal contribution
posted on 2024-02-27, 19:26authored byGyuntae Bae, Georgy Berezhnoy, Alejandra Flores, Claire Cannet, Hartmut Schäfer, Marc H. Dahlke, Patrick Michl, Markus W. Löffler, Alfred Königsrainer, Christoph Trautwein
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.