Metabolomics to Reveal Diagnostic Biomarkers in CA19-9 Negative Pancreatic Ductal Adenocarcinoma: A Cross-Sectional Study.

Pancreatic ductal adenocarcinoma (PDAC) with negative carbohydrate antigen 19-9 (CA19-9) lacks effective diagnostic and monitoring indicators. We aimed to identify metabolic characteristics in such patients through metabolomics and explored potential plasma biomarkers. In this study, untargeted metabolomics analysis was performed on plasma samples from 30 healthy controls and 30 CA19-9 positive and 30 CA19-9 negative PDAC patients by using liquid chromatograph-mass spectrometer (LC-MS) technology. Compared with healthy controls, 36 differential metabolites were upregulated, and 3 differential metabolites were downregulated in the plasma of CA19-9 negative PDAC patients. Four upregulated differential metabolites, including palmitic amide, dolichol phosphate, cholesteryl acetate, and vitamin A2 aldehyde, were potential biomarkers for diagnosing CA19-9 negative PDAC patients. Enrichment analysis of KEGG pathways showed that glycine and threonine metabolism, tyrosine and tryptophan biosynthesis, thiamine metabolism, etc., were disrupted in CA19-9 negative PDAC patients. In summary, we determined the metabolic heterogeneity in PDAC patients with normal CA19-9 levels. The detected metabolic biomarkers may offer new approaches for the clinical early diagnosis of CA19-9 negative PDAC in the future.