Abstract 4427: Do changes in lipid metabolism link obesity to pancreatic cancer
Authors: Rita Ghosh, Deepa Ajit, Jillian Woodworth, Danielle Fritze, Francisco G. Cigarroa, Glenn A. Halff, Addanki Pratap Kumar
Journal: Cancer Research (2024)

Abstract The near equal incidence and mortality rates of pancreatic cancer, combined with projections that pancreatic cancer will become the second-most common cancer-related deaths by 2050, underscore the need to identify patients with early disease and interrupt this trajectory. Obesity, weight gain and waistline have been implicated in increasing the risk of pancreatic cancer. Although metabolomic analyses of pancreatic cancer patients have established correlations between phospholipids, lysophospholipids with treatment outcomes, the association between metabolites, obesity, and pancreatic cancer remains largely understudied. The objective of this pilot study was to determine differences in serum metabolites in obese and overweight pancreatic cancer patients compared with healthy non-obese subjects. Our long-term goal is to develop serum marker(s) that may be used to prevent advanced pancreatic cancer and thus improve outcomes for these patients. Serum was obtained from healthy subjects (n=11; BMI range from 18-25), overweight (n=9; 25-30) and obese (n=7; &amp;gt;30) pancreatic cancer patients from an IRB approved study. Males (n=12) and females (n=15) were represented in the study. Global metabolic profiles were determined using Ultrahigh performance liquid chromatography-tandem mass spectroscopy. Raw data was extracted, peaks were identified and processed at Metabolon using the Laboratory Information Management System. Comparison between overweight pancreatic cancer patients and healthy controls identified 403 biochemicals (111 upregulated and 292 downregulated; p &amp;lt;0.05) and 93 biochemicals (40 upregulated and 53 downregulated; 0.05&amp;lt;p&amp;lt;0.10). Comparison of the differences in biochemicals between obese pancreatic cancer patients and healthy controls showed changes in 293 biochemicals (71 upregulated and 222 downregulated; p &amp;lt;0.05) and 123 biochemical changes at 0.05&amp;lt;p&amp;lt;0.10 (42 increased and 81 decreased). 38 (p &amp;lt;0.05) and 47 (0.05&amp;lt;p&amp;lt;0.10) differential levels of biochemicals were identified when obese and overweight pancreatic cancer patients were compared. Random forest analysis showed that the 30 top ranking biochemicals were involved in lipid metabolism, amino acid metabolism, nucleotide metabolism, peptide, xenobiotics, and carbohydrate metabolism. These data suggest an association between changes in lipid metabolism may be another link between obesity and pancreatic cancer. This project was funded in part by VA-Merit Award (I01 BX003876). Citation Format: Rita Ghosh, Deepa Ajit, Jillian Woodworth, Danielle Fritze, Francisco G. Cigarroa, Glenn A. Halff, Addanki Pratap Kumar. Do changes in lipid metabolism link obesity to pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4427.