ADP-ribosylation Levels Correlate with Gene Expression Patterns and Clinical Outcomes in Ovarian Cancers

Inhibitors of nuclear poly(ADP-ribose) polymerase (PARP) enzymes (e.g., PARP-1) have improved clinical outcomes in ovarian cancer, especially in patients with BRCA1/2 gene mutations or additional homologous recombination (HR) DNA repair pathway deficiencies. These defects serve as biomarkers for response to PARP inhibitors (PARPi). We sought to identify an additional biomarker that could predict responses to both conventional chemotherapy and PARPi in ovarian cancers. We focused on cellular ADP-ribosylation (ADPRylation), which is catalyzed by PARP enzymes and detected by detection reagents we developed previously. We determined molecular phenotypes of 34 high-grade serous ovarian cancers and associated them with clinical outcomes. We used our recombinant antibody-like ADP-ribose detection reagents to characterize the levels and patterns of ADP-ribosylation in a cohort of ovarian cancer tumor tissue samples and relate the results to molecular, cellular, and clinical outcomes.