Autoantibodies, antigen-autoantibody complexes and antigens complement CA125 for early detection of ovarian cancer

• Published in: British journal of cancer Vol. 130; no. 5; pp. 861 - 868
• Main Authors: Young Han, Chae, Bedia, Jacob S., Yang, Wei-Lei, Hawley, Sarah J., Bergan, Lindsay, Hopper, Marika, Celestino, Joseph, Guo, Jing, Gornet, Terrie G., Soosaipillai, Antoninus, Yang, Hailing, Doskocil, Samantha D., Lokshin, Anna E., Handy, Beverly C., Diamandis, Eleftherios P., Moore, Richard G., Lu, Karen H., Lu, Zhen, Anderson, Karen S., Drescher, Charles W., Skates, Steven J., Bast, Robert C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.03.2024; Nature Publishing Group
• Subjects: 692/53; 692/53/2421; Antigens; Autoantibodies; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cancer Research; Drug Resistance; Epidemiology; Molecular Medicine; Oncology; Osteopontin; Ovarian cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-023-02560-z

Background Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer. Methods Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers ( n  = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone. Results Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity. A four-biomarker panel including CA125, HE4, HE4 Ag-AAb and osteopontin detected 75% of early stage cancers in the validation set from among healthy controls compared to 62% with CA125 alone ( p  = 0.003) at 98% specificity. The same panel increased sensitivity for distinguishing early-stage ovarian cancers from benign pelvic masses by 25% ( p  = 0.0004) at 95% specificity. From 21 autoantibody candidates, 3 AAb (anti-p53, anti-CTAG1 and annt-Il-8) detected 22% of early stage ovarian cancers, potentially lengthening lead time prior to diagnosis. Conclusion A four biomarker panel achieved greater sensitivity at the same specificity for early detection of ovarian cancer than CA125 alone.