Abstract LB042: Elucidating plasma bacterial and host derived metabolites unique to epithelial ovarian cancer

Abstract The purpose of this study was to examine plasma metabolite profiles of women with epithelial ovarian cancer (EOC) to identify bacterial- and host-derived metabolites and pathways associated with this disease. EOC is highly curative if detected early, yet the majority of cases are diagnosed during late stages, decreasing survival rates. Despite advances in precision oncology, effective EOC early disease screening tests remain limited. Dynamic metabolic crosstalk in the tumor microenvironment (TME) is shown to support cancer progression. Current research suggest that bacterial metabolites enter the systemic circulation and alter the TME. Thus, understanding plasma metabolomic characteristics of EOC could present an opportunity for less invasive testing that allows for early detection. Using liquid chromatography-tandem mass spectroscopy, global metabolomic profiles were generated from biobanked plasma samples of women in four experimental groups including EOC (n=10), benign gynecologic diseases (n=10), non-EOC solid tumors (n=10), and healthy controls (n=10). Plasma samples were analyzed using a global discovery metabolomic platform. Statistical analysis of log-transformed, median scaled and minimum imputed data was approached through a one-way ANOVA to identify biochemicals that differed significantly between experimental groups. There were a total of 1, 204 known biochemicals identified in the samples. Patients with EOC had the largest number (335) of statistically significant (p ≤ 0. 05) biochemical differences (238 upregulated, 97 downregulated) compared to healthy controls than the other groups. Patients with EOC had elevated β-oxidation, decreased levels of key phospholipids and short/medium chain fatty acids, and increased endocannabinoids. By principal component analysis, the EOC group exhibited greater separation from the control group than the other groups. Top enriched pathways among patients with EOC compared to healthy controls primarily consisted of lipid pathways but also uniquely included those associated with glutathione metabolism (g-glutamyl amino acids), vitamin A metabolism, benzoate metabolism, and purine metabolism. The number of benzoates including hippurate, benzoate, and 3-phenylpropionate (hydrocinnamate) were significantly (p ≤ 0. 05) lower in the EOC group compared to healthy controls. The EOC group findings are suggestive of impaired cell turnover and potentially relate to inflammation regulation changes. Reduced levels of benzoate-associated metabolites suggest potential disruptions of gut bacteria, further distinguishing the EOC metabolic profile from the other groups. Larger patient cohorts comparing early versus late stage disease may provide indications of which pathways drive cancer progression and which serve as the consequence. Citation Format: Diane E. Mahoney, Ilce Medina-Meza. Elucidating plasma bacterial and host derived metabolites unique to epithelial ovarian cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr LB042.