Glycovariants of CA-125 for early detection of ovarian cancer
Principal Investigator
Name
Andrew Vickers
Degrees
PhD
Institution
Memorial Sloan Kettering Cancer Center
Position Title
Attending Research Methodologist
Email
vickersa@mskcc.org
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
2025-0037
Initial CDAS Request Approval
Jun 12, 2025
Title
Glycovariants of CA-125 for early detection of ovarian cancer
Summary
Large randomized trials, including the PLCO trial and UKCTOCS trial, have demonstrated that screening strategies based on CA-125 do not reduce ovarian cancer mortality, highlighting important limitations of current biomarker approaches and the need for alternative analytical strategies.
One promising area of investigation is the molecular heterogeneity of CA-125, particularly variation arising from cancer-associated glycosylation. Ovarian cancer is known to be associated with distinct alterations in glycosylation of the MUC16/CA-125 protein, including increased sialylation, core fucosylation, and the expression of truncated glycans such as Tn and sialyl-Tn, which are largely absent in benign conditions. These cancer-associated glycoforms have been proposed as a potential source of additional biological information beyond total CA-125 concentration.
Recent advances in assay technologies have enabled more robust and sensitive characterization of CA-125 glycovariants. Such approaches have demonstrated improved performance in distinguishing malignant from benign ovarian conditions, particularly in clinically challenging settings such as patients with borderline or moderately elevated CA-125 levels. Differences in glycovariant expression have also been observed across histological subtypes and disease characteristics, suggesting that these molecular features may reflect underlying tumor biology.
Despite these advances, the role of CA-125 glycovariants in broader clinical contexts, including their variability over time and their behaviour in longitudinally collected samples, remains incompletely understood. In particular, it is unclear to what extent glycovariant patterns are stable, reproducible, and informative across different stages of disease development or patient subgroups.
Longitudinal biospecimen resources such as the PLCO trial provide a unique opportunity to further investigate these questions in a well-characterized population setting. Analyses in such cohorts may help to better understand the temporal behaviour, variability, and potential clinical relevance of CA-125 glycovariants, and to inform future research on biomarker-based approaches for ovarian cancer.
The investigators previously used data from the PLCO in the development of the 4Kscore, a test used in prostate cancer diagnosis in over 75,000 US men per year. In other words, the investigators have a track record of conducting marker studies on PLCO samples and turning the results into markers that are used clinically to improve patient care.
Aims
1. To characterize selected CA-125 glycovariants in retrospective PLCO serum samples and assess their analytical performance and reproducibility across different sample subsets.
2. To evaluate the relationship between CA-125 glycovariant measurements and established clinical variables, including diagnostic groups, histological subtypes, and disease characteristics.
3. To investigate longitudinal variation of CA-125 glycovariants within individuals over time, including assessment of intra-individual variability and temporal stability.
4. To explore whether combinations of glycovariant measurements and conventional CA-125 provide additional descriptive information in different clinical contexts, including subgroups defined by baseline CA-125 levels or other clinical or parameters, and assess whether such combined testing could have the potential to improve survival outcomes of ovarian cancer patients.
Collaborators
Andrew Vickers (Memorial Sloan Kettering Cancer Center)
Hans Lilja (Memorial Sloan Kettering Cancer Center)
Kara Long Roche (Memorial Sloan Kettering Cancer Center)