Abstract 2253: Plasma metabolomic profiles associated with early and late-stage high-grade serous ovarian cancer
Authors: Sasamoto Naoko , Zeleznik Oana A. , Vitonis Allison F. , Cramer Daniel W. , Avila-Pacheco Julian , Clish Clary B. , Tworoger Shelley S. , Terry Kathryn L. 
Published: June 2022

Abstract
Background: Ovarian cancer has poor survival due to more than 60% of patients being diagnosed at advanced stage. Therefore, discovery of novel, non-invasive early detection biomarkers has high potential to improve survival. Here, we identified plasma metabolomic profiles associated with early-stage and late-stage high-grade serous ovarian cancer (HGSOC), the most common histotype.
Method: We examined 197 lipid and lipid-related metabolites measured using a validated, liquid chromatography tandem mass spectrometry method (Broad Institute, Cambridge, MA) in plasma collected prior to surgery from 40 early-stage and 40 late-stage HGSOC patients and 40 population-based controls matched on age, year, and menopausal status at blood draw. We used multivariable logistic regression, adjusted for matching factors, tubal ligation, oral contraceptive use, and parity, to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of ovarian cancer risk per 1 standard deviation increase in probit-transformed metabolite levels. We used Metabolite Set Enrichment Analysis (MSEA) to identify metabolite groups. We accounted for testing multiple correlated hypotheses using the number of effective tests (NEF) or false discovery rate (FDR).
Results: Compared to controls, there were 34 metabolites associated with early-stage HGSOC and 88 metabolites associate with late-stage HGSOC (unadjusted p-value&lt;0.05). All metabolites associated with risk of early-stage HGSOC and majority (n=80, 90%) of the metabolites associated with risk of late-stage HGSOC were inversely associated with ORs ranging from 0.28 to 0.48 for early-stage and 0.08 to 0.59 for late-stage HGSOC. Interestingly, the direction of association across all these metabolites were similar in both early-stage and late-stage HGSOC, with stronger effect estimates for late-stage HGSOC. After multiple testing correction, there were 9 statistically significant metabolites associated with risk of late-stage HGSOC (NEF p-value&lt;0.05) whereas no individual metabolites remained associated with risk of early-stage HGSOC. MSEA revealed similar patterns of association compared to controls across the 11 lipid groups assessed in early and late-stage HGSOC cases. Metabolite groups of phosphatidylethanolamine plasmalogens and triglycerides were inversely associated with early-stage HGSOC compared to controls (FDR p-value&lt;0.05). Metabolite groups of phosphatidylethanolamine plasmalogens and phosphatidylcholines were inversely, and diglycerides were positively associated with late-stage HGSOC compared to controls (FDR p-value&lt;0.05).
Conclusion: Our results revealed early-stage and late-stage HGSOC having similar plasma metabolomic profiles overall although there were more metabolites that were significantly associated with late-stage HGSOC than early-stage HGSOC compared to population-based controls.
Citation Format: Naoko Sasamoto, Oana A. Zeleznik, Allison F. Vitonis, Daniel W. Cramer, Julian Avila-Pacheco, Clary B. Clish, Shelley S. Tworoger, Kathryn L. Terry. Plasma metabolomic profiles associated with early and late-stage high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2253.