Evaluation of paraneoplastic antigens reveals TRIM21 autoantibodies as biomarker for early detection of ovarian cancer in combination with autoantibodies to NY-ESO-1 and TP53

Article type: Research Article

Authors: Hurley, Laura C.^a | Levin, Nancy K.^{a; c} | Chatterjee, Madhumita^{a; c} | Coles, Jasmine^a | Muszkat, Shlomo^a | Howarth, Zachary^a | Dyson, Gregory^{a; c} | Tainsky, Michael A.^{a; b; c; *}

Affiliations: [a] Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA | [b] Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI, USA | [c] Molecular Therapeutics Program, Karmanos Cancer Institute, Detroit, MI, USA

Correspondence: [*] Corresponding author: Michael A. Tainsky, Molecular Therapeutics Program, Karmanos Cancer Institute, 4100 John R, Detroit, MI 48201, USA. Tel.: +1 313 578 4340; Fax: +1 313 578 4316; E-mail: [email protected].

Abstract: BACKGROUND: The majority of ovarian cancer cases are diagnosed at an advanced stage with poor prognosis. This study evaluates autoantibodies against tumor antigens to identify candidate biomarkers for early detection of ovarian cancer in women at increased risk. OBJECTIVE: To assess the immunoreactivity of paraneoplastic antigens and tumor associated antigens with high-grade serous ovarian cancer (HGSOC) samples. METHODS: Five paraneoplastic antigens along with three tumor-associated antigens were evaluated with HGSOC patient serum samples. Validation screening was performed with n= 164 serum samples consisting of: 50 late stage HGSOC, 14 early stage HGSOC, 50 benign ovarian cyst, and 50 healthy control samples on ELISA and western blot. The four markers TRIM21, NY-ESO-1, TP53, and PAX8 were evaluated on a second validation serum set, n= 150. RESULTS: TRIM21 achieved the highest sensitivity in the first validation screening of 33% with 100% specificity. Combining TRIM21 with NY-ESO-1, TP53, and PAX8 provided 67% sensitivity with 94% specificity, and 56% sensitivity at 98% specificity. These four markers resulted in 46% sensitivity with 98% specificity in the second validation cohort; TRIM21 achieved the highest individual sensitivity of 36%. CONCLUSIONS: Autoantibodies to TRIM21, NY-ESO-1, and TP53 may complement CA125 in screening of women at genetic risk for ovarian cancer.

Keywords: Autoantibody, biomarker, ovarian cancer, paraneoplastic antigen

DOI: 10.3233/CBM-190988

Journal: Cancer Biomarkers, vol. 27, no. 3, pp. 407-421, 2020