Discovery and preliminary validation of a new panel of personalized ovarian cancer biomarkers for individualized detection of recurrence

Abstract

Background: Following first-line treatment, over 80% of advanced ovarian cancer cases suffer recurrence. Treatment of patients with recurrence based on CA125 has not resulted in improvements in outcome postulating that we need biomarkers for earlier detection. A tumor-specific array of serum proteins with advanced proteomic methods could identify personalized marker signatures that detect relapse at a point where early intervention may improve outcome. Methods: For our discovery phase, we employed the proximity extension assay (PEA) to simultaneously measure 1,104 proteins in 120 longitudinal serum samples (30 ovarian cancer patients). For our validation phase, we used PEAs to concurrently measure 644 proteins (including 21 previously identified candidates, plus CA125 and HE4) in 234 independent, longitudinal serum samples (39 ovarian cancer patients). Results: We discovered 23 candidate personalized markers (plus CA125 and HE4), in which personalized combinations were informative of recurrence in 92% of patients. In our validation study, 21 candidates were each informative of recurrence in 3-35% of patients. Patient-centric analysis of 644 proteins generated a refined panel of 33 personalized tumor markers (included 18 validated candidates). The panel offered 91% sensitivity for identifying individualized marker combinations that were informative of recurrence. Conclusion: Tracking individualized combinations of tumor markers may offer high sensitivity for detecting recurrence early and aid in prompt clinical referral to imaging and treatment interventions.