Abstract 249P
Background
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, characterized by challenging diagnosis and limited treatment options. Metabolic reprogramming has emerged as a pivotal factor in tumor initiation, progression, and therapy resistance. Understanding the metabolic regulation of PDAC cells not only enhances our comprehension of disease mechanisms but also provides insights for developing new diagnostic and therapeutic strategies.
Methods
We conducted non-targeted metabolomics analysis on samples from 30 PDAC patients and distal pancreatic tissues to explore PDAC metabolism comprehensively.
Results
We identified a total of 315 differential metabolites, including significantly up-regulated and down-regulated ones. Key positively ionized metabolites with significantly increased expression included hydrocortisone 21-acetate, Zaleplon, and 1-methyl-3-isobutylxanthine, whereas those with decreased expression were Ile-Arg, 1-palmitoyl-2-linoleoyl-rac-glycerol, and N-oleoyl-d-erythro-sphingosylphosphorylcholine. Among negatively ionized metabolites, up-regulated ones included Erdosteine thioacid, 2-hydroxylamino-4,6-dinitrotoluene, while down-regulated ones were Trp-Val, Thr-Val-Leu, and Val-Gly-Va. KEGG analysis indicated enrichment of differential metabolites in pathways such as central carbon metabolism in cancer, protein digestion and absorption, glycine, serine, and threonine metabolism, ABC transporters, and amino acid biosynthesis. Pathway activity analysis using differential abundance scores highlighted significant upregulation in pathways including pantothenate and CoA biosynthesis, insulin resistance, beta-alanine metabolism, and bile secretion. KEGG pathway network analysis identified ABC transporters, amino acid biosynthesis, central carbon metabolism in cancer, protein digestion and absorption, and glycine, serine, and threonine metabolism as central nodes.
Conclusions
Our findings reveal distinct metabolic profiles in PDAC that potentially influence disease development through metabolites and metabolic pathways. These insights underscore the potential for targeting metabolic features in PDAC treatment strategies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Key research and development project in Hunan Province (China) in 2024 (grant number: 2024JK2111).
Disclosure
All authors have declared no conflicts of interest.