{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:22:27Z","timestamp":1790882547034,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T00:00:00Z","timestamp":1573516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP160145"],"award-info":[{"award-number":["RP160145"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2020,2,15]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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\u2010stage (I\/II) disease. Sensitivity might be improved through the combination of CA 125 with other biomarkers. Among potential biomarkers, antigen\u2010autoantibody (Ag\u2010AAb) complexes have received relatively little attention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Luminex\u2010based immunoassays were used to measure human epididymis protein 4 (HE4), anti\u2010HE4 autoantibody, and HE4 Ag\u2010AAb complexes in sera from patients with early\u2010 (n\u00a0=\u00a073) and late\u2010stage ovarian cancers (n\u00a0=\u00a049) at the time of diagnosis and from asymptomatic women with (n\u00a0=\u00a015) or without ovarian cancer (n\u00a0=\u00a0212) enrolled in the Normal Risk Ovarian Cancer Screening Study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At 98% specificity for healthy, asymptomatic women, 7% of patients with early\u2010stage (I\/II) ovarian cancer and 4% of patients with late\u2010stage (III\/IV) disease had elevated levels of HE4 autoantibody, whereas elevated levels of HE4 Ag\u2010AAb complexes were detected in sera from 38% of early\u2010stage cases and 31% of late\u2010stage cases. Complementarity was observed in receiver operating characteristic (ROC) curves between HE4 Ag\u2010AAb complexes and CA 125 levels in early\u2010stage ovarian cancer (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.001). CA 125 detected 63% of cases, and a combination of CA 125 and HE4 Ag\u2010AAb complexes detected 81%. Complementarity was also observed in ROC curves for an independent validation set with 69 early\u2010stage patients (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.039). HE4 Ag\u2010AAb 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HE4 Ag\u2010AAb complexes could complement CA 125 in detecting a higher fraction of early\u2010stage ovarian cancers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.32582","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T09:30:56Z","timestamp":1573551056000},"page":"725-736","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Human epididymis protein 4 antigen\u2010autoantibody complexes complement cancer antigen 125 for detecting early\u2010stage ovarian cancer"],"prefix":"10.1002","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6559-0556","authenticated-orcid":false,"given":"Wei\u2010Lei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center Houston Texas"},{"name":"Odyssey Program The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center Houston Texas"},{"name":"Department of Obstetrics and Gynecology Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan M.","family":"Fellman","sequence":"additional","affiliation":[{"name":"Department of Biostatistics The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5289-331X","authenticated-orcid":false,"given":"Jing","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Biostatistics The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen H.","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usha","family":"Menon","sequence":"additional","affiliation":[{"name":"University College London London 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