Abstract
Abstract INTRODUCTION: Biomarkers for early detection as well as disease stratification are a major area of focus in prostate cancer (CaP) research. Autoantibodies against a large array of tumor associated antigens (TAAs) have been noted in a diverse number of cancers, including CaP. Since autoantibodies represent humoral responses elicited in response to TAAs expressed in tumor cells, it is likely that autoantibodies could serve as diagnostic/prognostic markers for CaP. Hence, the present study addresses the following: i) Are autoantibodies against ERG, an oncogene frequently overexpressed in CaP, present in the sera of patients?; ii) Does a multiplex autoantibody panel containing ERG, AMACR, C-MYC, and HERV-K Gag improve the detection of CaP? METHODS: Sera from 50 CaP patients positive for ERG expression and 50 patients negative for ERG expression, along with 50 healthy control subjects were analyzed. Purified recombinant protein for ERG, AMACR, and C-MYC as well as synthetic peptides corresponding to epitopes in ERG and HERV-K Gag were used in an enzyme-linked immunosorbent assay (ELISA) developed in our laboratory to detect autoantibodies in the sera of CaP patients. In addition, a luciferase immunoprecipitation assay (LIPS), involving a chimeric luciferase-ERG protein, was used as an independent assay to test the presence of anti-ERG autoantibodies. RESULTS: Analysis of patient sera by ELISA revealed significantly higher detection of autoantibodies against ERG (P = 0.0001), AMACR (P < 0.0001), C-MYC (P = 0.0013), and HERV-K Gag (P < 0.0001) proteins in CaP cases compared to healthy controls. The specificity of anti-ERG autoantibodies was supported by a competitive ELISA assay. Further, the LIPS assay was also able to detect anti-ERG autoantibodies in patient sera. In addition, a multiplex panel assay involving ERG, AMACR, and HERV-K Gag greatly improved the detection of true positive CaP cases (AUC = 0.792). CONCLUSIONS: Here we demonstrated that autoantibodies against ERG are present in the sera of prostate cancer patients through ELISA analysis. In addition, utilizing a panel of genes for autoantibody detection, consisting of ERG, AMACR, and HERV-K Gag, showed high specificity for CaP cases. These promising findings suggest the diagnostic potential of autoantibodies and similar autoantibody panels in enhancing CaP diagnosis. Source of Funding: Center for Prostate Disease Research, Uniformed Services University Grant HU0001-10-2-0002, NCI/EDRN Grant ACN12011-001-0, and the National Cancer Institute Grant R01CA162383. Citation Format: Anshu Rastogi, Amina M. Ali, Sreedatta Banerjee, Lakshmi Ravindranath, Gyorgy Petrovics, Shyh-Han Tan, Jennifer Cullen, Yongmei Chen, Denise Young, Isabell A. Sesterhenn, Jacob Kagan, Sudhir Srivastava, David G. McLeod, Shiv Srivastava, Alagarsamy Srinivasan. Immunobiomarkers: novel autoantibody panel comprising oncogenic ERG, C-MYC, AMACR and HERV-K Gag for the detection of prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4958.
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