Abstract A005: Novel glycoproteomic biomarkers for early detection of ovarian cancer

Abstract Introduction: Ovarian cancer remains the most fatal gynecologic malignancy. This grim reality stems primarily from the absence of effective early detection methods, resulting in most women receiving diagnoses at advanced stages. Unfortunately, current screening strategies for healthy, asymptomatic women have yet to be successfully established. CA-125, considered the gold standard, falls short due to insufficient sensitivity and specificity. This critical gap underscores an urgent need for novel, highly accurate biomarkers that can detect the disease at its earliest stages across diverse populations. Glycoproteins, known to undergo significant alterations in early disease states, represent a promising class of biomarkers for early cancer detection and screening capabilities. Methods: Leveraging our high throughput glycoproteomics platform, we conducted a comprehensive analysis of serum samples from a prospectively collected clinical study (WIRB IRB 20190246, 20221935) including women with ovarian cancer (OvCa n=116), benign pelvic mass findings (n=82), and healthy controls (n=78). Samples from MD Anderson were used to externally validate with early-stage OvCa (Stage I/II, n=89), benign pelvic mass findings (n=106), and healthy controls (n=112). Serum samples were assessed by InterVenn’s targeted mass spectrometry platform and 38 peptides and glycopeptides were quantified. A previously-locked classifier to predict malignancy was evaluated in this hold-out validation cohort. Results: Our analysis utilized a novel signature comprising 16 peptides and glycopeptides that demonstrate significant differentiation in early-stage OvCa patients compared to both benign and healthy cohorts. This glycoproteomic signature achieved high diagnostic performance, exhibiting a specificity of 90% and 76% for healthy and benign patients, 64% sensitivity for stage I and II OvCa and 73% for all OvCa patients. External validation exhibited a specificity of 96% and 75% for healthy and benign patients, respectively, and a sensitivity of 64% for early-stage OvCa, respectively. Conclusion: This study demonstrates the significant potential of a novel glycoproteomic biomarker signature for the accurate and non-invasive detection of early-stage ovarian cancer. The high sensitivity and specificity observed suggest that this liquid biopsy-based assay could serve as a powerful tool for population-wide screening, enabling earlier diagnosis, facilitating timely intervention, and ultimately improving patient survival outcomes for this devastating disease. Further prospective validation in larger cohorts is warranted. Citation Format: Khushbu Desai, Kaitlynn Moser, Elizabeth Quach, Meghan Grech, Rachel Rice, Daniel Serie, Andrew Quong, Robert C. Bast. Novel glycoproteomic biomarkers for early detection of ovarian cancer abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85 (18Suppl): Abstract nr A005.