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Osteopontin, Macrophage Migration Inhibitory Factor and Anti-Interleukin-8 Autoantibodies Complement CA125 for Detection of Early Stage Ovarian Cancer

1
Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
2
Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
3
Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
4
Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
5
Department of Epidemiology, Pathology, Medicine, and Obstetrics/Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(5), 596; https://doi.org/10.3390/cancers11050596
Received: 1 April 2019 / Revised: 18 April 2019 / Accepted: 24 April 2019 / Published: 28 April 2019
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Abstract

Early detection of ovarian cancer promises to reduce mortality. While serum CA125 can detect more than 60% of patients with early stage (I–II) disease, greater sensitivity might be observed with a panel of biomarkers. Ten protein antigens and 12 autoantibody biomarkers were measured in sera from 76 patients with early stage (I–II), 44 patients with late stage (III–IV) ovarian cancer and 200 healthy participants in the normal risk ovarian cancer screening study. A four-biomarker panel (CA125, osteopontin (OPN), macrophage inhibitory factor (MIF), and anti-IL-8 autoantibodies) detected 82% of early stage cancers compared to 65% with CA125 alone. In early stage subjects the area under the receiver operating characteristic curve (AUC) for the panel (0.985) was significantly greater (p < 0.001) than the AUC for CA125 alone (0.885). Assaying an independent validation set of sera from 71 early stage ovarian cancer patients, 45 late stage patients and 131 healthy women, AUC in early stage disease was improved from 0.947 with CA125 alone to 0.974 with the four-biomarker panel (p = 0.015). Consequently, OPN, MIF and IL-8 autoantibodies can be used in combination with CA125 to distinguish ovarian cancer patients from healthy controls with high sensitivity. Osteopontin appears to be a robust biomarker that deserves further evaluation in combination with CA125. View Full-Text
Keywords: ovarian cancer; osteopontin (OPN); macrophage migration inhibitory factor (MIF); CA125; IL-8 autoantibodies (IL-8 AAb); early detection ovarian cancer; osteopontin (OPN); macrophage migration inhibitory factor (MIF); CA125; IL-8 autoantibodies (IL-8 AAb); early detection
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Guo, J.; Yang, W.-L.; Pak, D.; Celestino, J.; Lu, K.H.; Ning, J.; Lokshin, A.E.; Cheng, Z.; Lu, Z.; Bast, R.C., Jr. Osteopontin, Macrophage Migration Inhibitory Factor and Anti-Interleukin-8 Autoantibodies Complement CA125 for Detection of Early Stage Ovarian Cancer. Cancers 2019, 11, 596.

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