Abstract 6379: Comparison of lipid profiles in children with solid tumors receiving chemotherapy and healthy children

Abstract Background: Lipid metabolism plays an important role in the regulation of synaptic function and plasticity.Cancer chemotherapy (chemo) can disturb the lipid profile, potentially linked with neuropsychological toxicities. This study aimed to compare the lipid profiles between children with cancer receiving chemo and healthy children. Methods: A prospective, observational study was conducted in 21 children with solid tumors enrolled from Children’s Healthcare of Atlanta (CHOA) and 16 controls. Children with solid tumors were consented precycle 2 chemo (T1) and followed at the end of chemo (T2). Controls completed one timepoint of data collection. At T1 (n=21) and T2 (n=13), fecal samples were collected for lipidomics analysis. Fecal lipids were processed using a high-resolution, untargeted lipidomics LC-MS approach. MetaboAnalyst and linear mixed models were used to analyze the data with false discovery rate correction (FDR 0.2). Results: There were no significant differences in age, sex, race, and body mass index between the groups. In total 241 lipid features were identified with high confidence and analyzed. A comparison between children with solid tumors at T2 (n=12) vs. controls (n=16) detected 8 differential lipids, which can be clustered into 4 classes, including 4 triglycerides (TG), 2 phosphatidylcholine (PC), 1 sphingomyelin (SM), and 1 lysophosphatidylcholine (LPC). Additionally, 24 differential lipids were detected for children with solid tumors from T1 to T2 (n=12), including 6 classes: 9 SM, 7 PC, 3 diacylglycerols (DG), 2 TG, 2 monoacylglycerols (MG), and 1 phosphatidylethanolamine (PE). Compared with controls, children with solid tumors at T2 had higher levels of SM (e.g., SM(d36:1)) and lower levels of TG (e.g., TG(18:0/18:0/20:0)), LPC (e.g., LPC(20:4)), and PC (e.g., PC(33:4). Compared with children at T1, those at T2 had higher levels of SM (e.g., SM(d36:1)), PE (e.g., PE(16:0p/20:4), PC (e.g., PC(30:0), and PC(36:1)), and lower levels of TG (e.g., TG(18:0/18:0/20:0) and TG(18:0/16:0/18:0)), LPC (e.g., LPC(20:4)), DG (e.g., DG(18:0/16:0) and DG(18:0/18:0)), and MG (e.g., MG(18:0)). Conclusion: Children with cancer chemo had alterations in fecal lipid profiles impacting the metabolism of PC, SM, TG, PE, MG, and DG. The increased PC and the dysregulation of LPC in comparison with controls suggest the decreased activity of phospholipase A2 (PLA2), primarily reported in inflammatory disease. Altered activity of lysophospholipid acyltransferase (LPCAT), diacylglyceride acyltransferase (DGAT), and phosphatidylethanolamine methyl transferase (PEMT) could also explain changes in PC and glycerolipids. Combined, these suggest dysregulation of the Kennedy or Lands pathways towards PC synthesis. Future work is needed to study whether the disturbed lipid metabolisms were associated with treatment toxicities and outcomes such as cognitive dysfunction based on literature. Citation Format: Jinbing Bai, Madelyn Houser, Melissa Martin, Christie Powell, Kristal Maner-Smith, Kathryn S. Sutton, Thomas Olson, Deborah W. Bruner. Comparison of lipid profiles in children with solid tumors receiving chemotherapy and healthy children [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 6379.