Abstract A057: Decreased plasma linoleic acid and increased oleic acid associated with obesity in pancreatic cancer
Authors: Kaylin M. Chasser, Martha A. Belury, Jordan M. Cloyd, Rachel M. Cole, Stacey Culp, Mary E. Dillhoff, Aslam Ejaz, Kristyn Gumpper-Fedus, Phil A. Hart, Lauren Kanzaki, Andrei V. Manilchuk, Anne M. Noonan, Timothy M. Pawlik, Mitchell Ramsey, Zobeida Cruz-Monserrate
Journal: Cancer Research (2024)

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that interferes with absorption of nutrients including fats. Obesity is a key risk factor for PDAC and confers metabolic dysfunction associated with changes in fatty acid (FA) metabolism, including FAs in the linoleic acid and palmitic acid pathways. In turn, FAs can influence the molecular signaling in pancreatic cells. Changes in blood FA abundance induced by PDAC could be amplified by obesity and influence PDAC-associated outcomes. Therefore, we investigated plasma FA abundance in patients with treatment-naïve PDAC compared with control participants and explored how obesity status affects the linoleic acid and palmitic acid pathways in cancer. Methods: Blood and clinical characteristics were collected from participants with resectable tumors (rPDAC, n=52) or metastatic disease (mPDAC, r=55) that were treatment-naïve and 22 controls. Plasma samples were analyzed for relative FA abundance using gas chromatography and levels were compared between controls, rPDAC and mPDAC. Changes in FA abundance due to obesity (body mass index ≥30 kg/m2) were assessed in all groups. All FA abundance changes were analyzed using a two-way ANOVA with the appropriate parametric or non-parametric test, and p-values were adjusted using the Bonferroni correction. Results: Compared with controls, both rPDAC and mPDAC were associated with increased FA abundance of palmitic acid and decreased abundance of linoleic acid, γ-linolenic acid, and dihomo-γ-linolenic acid, regardless of obesity status (p&amp;lt;0.05). Plasma FA abundance of linoleic acid was increased in mPDAC versus rPDAC, regardless of obesity status (p&amp;lt;0.05). Decreased abundance of linoleic acid was noted in rPDAC and mPDAC participants with obesity versus participants without obesity, while there was an increased abundance of oleic acid observed in mPDAC among participants with obesity versus participants without obesity (p&amp;lt;0.05). Conclusions: Plasma FA levels are dysregulated in all PDAC stages versus controls. The results suggest that obesity-associated metabolic dysregulation influences linoleic acid and oleic acid abundances of participants with treatment-naïve PDAC. By improving our understanding of how obesity influences FA abundance in PDAC, we can identify novel mechanistic targets for treatment specific to PDAC stage and obesity status. Citation Format: Kaylin M. Chasser, Martha A. Belury, Jordan M. Cloyd, Rachel M. Cole, Stacey Culp, Mary E. Dillhoff, Aslam Ejaz, Kristyn Gumpper-Fedus, Phil A. Hart, Lauren Kanzaki, Andrei V. Manilchuk, Anne M. Noonan, Timothy M. Pawlik, Mitchell Ramsey, Zobeida Cruz-Monserrate. Decreased plasma linoleic acid and increased oleic acid associated with obesity in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A057.