Abstract

Abstract Background: Early detection of ovarian cancer promises to reduce mortality. At present, only 20 percent of ovarian cancer is found in early stage (I-II). CA125 is found in sera from approximately 60% of patients with early stage disease. Greater sensitivity could be observed with a panel of blood tests. Methods: A panel of 10 antigen biomarkers (MIF, Leptin, IL-6, IL-8, TNFa, OPN, FGF2, HE4, TGFa and a panel of autoantibodies (AAbs) against 12 antigens (IL-8, MDM2, c-myc, PLAT, EpCAM, HOXA7, ENO1, PDI, HSPA5, HSPA8, ANXA2, Cathepsin D) were analyzed in sera of 77 ovarian cancer patients with early stage (I-II), 50 patients with late stage (III-IV), and 216 healthy women from the Normal Risk Ovarian Cancer Screening Study (NROSS) using Luminex-based immunoassays. Serum levels of serum tumor marker CA-125 were routinely measured in all patients using a Roche assay. The most promising markers (CA125, MIF, OPN, and anti-IL-8 autoantibodies were validated using an independent panel with sera from 69 early stage and 50 late ovarian cancer patients and 200 healthy controls. Result: Serum level of CA125, MIF, OPN and IL-8 AAb were elevated in early stage (I-II) and late stage (III-IV) ovarian cancer patients compared with healthy controls. Analyzing the positive biomarkers in combination with CA125 increased detection of early stage disease from 62% with CA125 alone to 92% a panel of CA125, MIF, OPN and IL-8 AAb at 98% specificity. For patients with late stage disease sensitivity increased from 90% to 98% with the panel. Complementarity of CA125 with MIF, OPN and IL-8 AAb was confirmed with an independent validation set, where sensitivity for early stage disease was improved from 84% to 91% at 98% specificity. Conclusion: MIF, OPN and IL8 AAb could be used in combination with CA125 to distinguish ovarian cancer patients from health controls with high sensitivity. Citation Format: Jing Guo, Wei-lei Yang, Joseph Celestino, Karen Lu, Anna E. Lokshin, Zhen Lu, Robert C. Bast. Macrophage inhibitory factor (MIF), osteopontin (OPN) and anti-interleukin-8 (IL-8) autoantibodies (AAb) complement CA125 for detection of early-stage ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 912.

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