Abstract 2338: Plasma proteomics associated with ovarian cancer risk in the Nurses' Health Studies

Abstract Background: While inflammation and gonadotropin levels are hypothesized to contribute to ovarian cancer initiation, specific proteomic pathways and other potential mechanisms are unclear. Thus, we aimed to identify novel blood-based non-invasive proteomic risk biomarkers for invasive epithelial ovarian cancer. Method: We measured 7, 310 pre-diagnostic plasma proteins using SomaScan v4.1 in 169 incident ovarian cancer cases [140 high-grade serous (HGS) cases] and 169 matched controls nested within the Nurses’ Health Studies. We excluded proteins with coefficient of variation ≥ 25% and influenced by delayed processing, resulting in 3, 131 proteins included in this analysis. We transformed protein levels to probit scores to achieve normality and used conditional logistic regression modeling to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) per one standard deviation increase in protein levels. We used Gene Set Enrichment Analysis to identify biological pathways and STRING to conduct protein-protein interaction network and functional enrichment analysis. We also conducted analyses restricted to HGS histotype. Results: All ovarian cancer cases included in the current analysis had blood samples collected years prior to diagnosis (median=14 years). Average age at blood collection was 56.3 years in both ovarian cancer cases and controls. When examining individual proteins associated with ovarian cancer risk, 94 proteins were significantly associated with ovarian cancer risk with nominal p-value<0.05. Biological pathway analysis revealed complement cascade (NES=2.0; FDR p=0.049) and innate immune system (NES=1.5; FDR p=0.049) pathways being upregulated in ovarian cancer cases compared to controls. STRING analysis showed protein-protein interactions were enriched in pathways such as tissue remodeling (e.g., COL6A1, COL18A1, IGFBP2), lipid metabolism (e.g., NCOA2, ME1), and B cell function (e.g., IGLL5, MZB1) in ovarian cancer cases compared to controls. Similar results were observed for HGS ovarian cancer. Discussion: We conducted a comprehensive examination of the plasma proteins associated with ovarian cancer risk in a prospective cohort study and observed upregulation of pathways related to innate immune system and complement cascade being associated with ovarian cancer risk. Citation Format: Nan Lin, Allison F. Vitonis, Simon T. Dillion, Ngo Long, Shelley S. Tworoger, Towia A. Libermann, Kathryn L. Terry, Naoko Sasamoto. Plasma proteomics associated with ovarian cancer risk in the Nurses' Health Studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2338.