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Human epididymis protein 4 antigen-autoantibody complexes complement cancer antigen 125 for detecting early-stage ovarian cancer

Yang, W-L; Lu, Z; Guo, J; Fellman, BM; Ning, J; Lu, KH; Menon, U; ... Bast, RC; + view all (2020) Human epididymis protein 4 antigen-autoantibody complexes complement cancer antigen 125 for detecting early-stage ovarian cancer. Cancer , 126 (4) pp. 725-736. 10.1002/cncr.32582. Green open access

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Abstract

Background: Early detection of ovarian cancer could significantly improve patient outcomes. Cancer antigen 125 (CA 125) is elevated in sera from approximately 60% of patients with early‐stage (I/II) disease. Sensitivity might be improved through the combination of CA 125 with other biomarkers. Among potential biomarkers, antigen‐autoantibody (Ag‐AAb) complexes have received relatively little attention. / Methods: Luminex‐based immunoassays were used to measure human epididymis protein 4 (HE4), anti‐HE4 autoantibody, and HE4 Ag‐AAb complexes 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. / Results: At 98% specificity for healthy, asymptomatic women, 7% of patients with early‐stage (I/II) ovarian cancer and 4% of patients with late‐stage (III/IV) disease had elevated levels of HE4 autoantibody, whereas elevated levels of HE4 Ag‐AAb complexes were detected in sera from 38% of early‐stage cases and 31% of late‐stage cases. Complementarity was observed in receiver operating characteristic (ROC) curves between HE4 Ag‐AAb complexes and CA 125 levels in early‐stage ovarian cancer (P < .001). CA 125 detected 63% of cases, and a combination of CA 125 and HE4 Ag‐AAb complexes detected 81%. Complementarity was also observed in ROC curves for an independent validation set with 69 early‐stage patients (P = .039). HE4 Ag‐AAb complexes were detected in serial preclinical serum samples from women destined to develop ovarian cancer: they correlated with CA 125 but did not provide a lead time. / Conclusions: HE4 Ag‐AAb complexes could complement CA 125 in detecting a higher fraction of early‐stage ovarian cancers.

Type: Article
Title: Human epididymis protein 4 antigen-autoantibody complexes complement cancer antigen 125 for detecting early-stage ovarian cancer
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/cncr.32582
Publisher version: https://doi.org/10.1002/cncr.32582
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: antigen‐autoantibody complexes, biomarkers, cancer antigen 125 (CA 125), early detection, human epididymis protein 4 (HE4), ovarian cancer
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10086488
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