Abstract

New Insights on Ovarian Cancer Biomarker CA125

Rebecca Whelan, Associate Professor of Chemistry, University of Kansas

There is an unmet need for innovative molecular tools that can assist in the clinical management of high-grade serous ovarian cancer. Improving the performance of validated biomarkers by reinventing their detection strategy is a compelling and underused approach to meet this need. The serum marker CA125 plays a crucial role in the clinical management of ovarian cancer, but, despite its importance, important questions remain regarding its molecular structure and role in cancer progression. Through a combination of long-read sequencing, bottom-up proteomics, AI-guided molecular structure prediction, and mutation analysis, the Whelan lab has recently developed a new model for the ovarian cancer biomarker CA125. This model will be described. The nature of the CA125 assay may contribute to ongoing disparities in ovarian cancer survivorship. Importantly, serum CA125 levels in Black women have been shown to be lower than levels in white women, but the molecular-level reasons for these racial differences are unknown. Current tests and algorithms employ a single CA125 cut-off value and do not consider racial/ethnic difference, which may contribute to the fact that Black ovarian cancer patients are diagnosed at later stage than white patients with concomitantly poorer clinical outcomes. Through targeted proteomics and long-read sequencing, the Whelan lab is investigating the racial differences in serum CA125 levels. Preliminary results on this project will be presented.