Predictive ability of novel glycovariant biomarkers of CA125 and CA15-3 up to three years prior to ovarian cancer diagnosis: a population-based case-control study.

内容摘要

Nanoparticle immunoassays for CA125 and CA15-3 glycovariants are promising tools for epithelial ovarian cancer (EOC) and borderline ovarian tumor (BOT) early detection. This retrospective population-based study utilized prospective (<&#x2009;3 years) plasma samples from 110 cases and 440 controls. Sialyl-Thomsen-nouveau (STn) antibody and macrophage galactose-type lectin (MGL) to detect cancer antigen 125 (CA125) and 15&#x2009;-&#x2009;3 (CA15-3) glycoforms were evaluated, using CA125, CA15-3, and HE4 enzyme immunoassay (EIA) references. The area under the receiver operating characteristic curve (AUC), partial AUC (pAUC) at specificities 0.9-1.0, and sensitivity (SN) at 0.98 specificity (SP) for detecting EOC/BOT were calculated. The single marker with the highest point estimate for pAUC and SN at 98% SP was CA125EIA (pAUC 0.71 (0.66, 0.76), SN at 98% SP 0.29 (0.17-0.42 combinations)). The CA15-3STn&#x2009;+&#x2009;CA125EIA and CA125EIA&#x2009;+&#x2009;HE4EIA improved the detection rate point estimates and provided the highest pAUC values (CA125EIA&#x2009;+&#x2009;CA15-3STn: 0.75 (0.70-0.80); CA125EIA&#x2009;+&#x2009;HE4EIA: 0.71 (0.66-0.77)). For 0-<1, 1-<2 and 2-<3 years lag time, CA125EIA and the CA125 glycovariants provided similar pAUC and SN at 98% SP, with largely overlapping confidence intervals. This case-control study, which used plasma samples collected up to three years before diagnosis of EOC or BOT, did not provide evidence of a higher discriminatory capacity of the glycovariant biomarkers compared with the clinically established biomarker CA125EIA in asymptomatic women. Increased plasma volumes and larger cohorts are suggested in future studies.