Comparison of candidate serologic markers for type I and type II ovarian cancer

Objective To examine the value of individual and combinations of ovarian cancer associated blood biomarkers for the discrimination between plasma of patients with type I or II ovarian cancer and disease-free volunteers. Methods Levels of 14 currently promising ovarian cancer-related biomarkers, including CA125, macrophage inhibitory factor-1 (MIF-1), leptin, prolactin, osteopontin (OPN), insulin-like growth factor-II (IGF-II), autoantibodies (AAbs) to eight proteins: p53, NY-ESO-1, p16, ALPP, CTSD, B23, GRP78, and SSX, were measured in the plasma of 151 ovarian cancer patients, 23 with borderline ovarian tumors, 55 with benign tumors and 75 healthy controls. Results When examined individually, seven candidate biomarkers (MIF, Prolactin, CA-125, OPN, Leptin, IGF-II and p53 AAbs) had significantly different plasma levels between type II ovarian cancer patients and healthy controls. Based on the receiver operating characteristic (ROC) curves constructed and area under the curve (AUC) calculated, CA125 exhibited the greatest power to discriminate the plasma samples of type II cancer patients from normal volunteers (AUC 0.9310), followed by IGF-II (AUC 0.8514), OPN (AUC 0.7888), leptin (AUC 0.7571), prolactin (AUC 0.7247), p53 AAbs (AUC 0.7033), and MIF (AUC 0.6992). p53 AAbs levels exhibited the lowest correlation with CA125 levels among the six markers, suggesting the potential of p53 AAbs as a biomarker independent of CA125. Indeed, p53 AAbs increased the AUC of ROC curve to the greatest extent when combining CA125 with one of the other markers. At a fixed specificity of 100%, the addition of p53 AAbs to CA125 increased sensitivity from 73.8% to 85.7% to discriminate type II cancer patients from normal controls. Notably, seropositivity of p53 AAbs is comparable in type II ovarian cancer patients with negative and positive CA125, but has no value for type I ovarian cancer patients. Conclusions p53 AAbs might be a useful blood-based biomarker for the detection of type II ovarian cancer, especially when combined with CA125 levels.