Active ratio test (Art) as a novel diagnostic for ovarian cancer

Background: Despite substantial effort, there remains a lack of biomarker-based, clinically relevant testing for the accurate, non-invasive diagnostic or prognostic profiling of epithelial ovarian cancers (EOC). Our previous work demonstrated that whilst the inflammatory marker C-X-C motif chemokine ligand 10 (CXCL10) has prognostic relevance in ovarian cancer, its use is complicated by the presence of multiple, N-terminally modified variants, mediated by several enzymes including Dipeptidyl Peptidase 4 (DPP4). Methods: In this study, we provide the first evidence for the “Ac-tive Ratio Test” (ART) as a novel method to measure biologically relevant CXCL10 proteoforms in clinical samples. Results: In a cohort of 275 patients, ART accurately differentiated patients with malignant EOCs from those with benign gynaecological conditions (AUC 0.8617) and significantly out-performed CA125 alone. Moreover, ART combined with the measurement of CA125 and DPP4 significantly increased prognostic performance (AUC 0.9511; sensitivity 90.0%; specificity 91.7%; Co-hen’s d > 1) for EOC detection. Conclusion: Our data demonstrate that ART provides a useful method to accurately discriminate between patients with benign versus malignant EOC, and highlights their relevance to ovarian cancer diagnosis. This marker combination may also be applicable in broader screening applications, to identify or discriminate benign from malignant disease in asymptomatic women.