Yang WL, Lu Z, Guo J, et al. - As sera from nearly 60% of patients with early-stage (I/II) disease exhibit elevated cancer antigen 125 (CA 125) and there is a possibility of improvement in sensitivity through the combination of CA 125 with other biomarkers, researchers here focused on potential biomarkers, namely antigen-autoantibody (Ag-AAb) complexes, that have received relatively little attention. Using Luminex-based immunoassays, human epididymis protein 4 (HE4), anti-HE4 autoantibody, and HE4 Ag-AAb complexes were determined in sera from patients with early- (n = 73) and late-stage ovarian cancers (n = 49) at the time of diagnosis and from asymptomatic women with (n = 15) or without ovarian cancer (n = 212) enrolled in the Normal Risk Ovarian Cancer Screening Study. Findings support the possible value of HE4 Ag-AAb complexes for complementing CA 125 in identifying a higher fraction of early-stage ovarian cancers. In receiver operating characteristic (ROC) curves, they observed complementarity between HE4 Ag-AAb complexes and CA 125 levels in early-stage ovarian cancer. Detection of 63% of cases was accomplished using CA 125, and 81% using a combination of CA 125 and HE4 Ag-AAb complexes. Serial preclinical serum samples from women destined to develop ovarian cancer also exhibited HE4 Ag-AAb complexes: they correlated with CA 125 but did not provide a lead time.