Autoantibodies against oncogenic ERG protein in prostate cancer: potential use in diagnosis and prognosis in a panel with C-MYC, AMACR and HERV-K Gag

Abstract

Overdiagnosis and overtreatment of prostate cancer (CaP) is attributable to widespread reliance on PSA screening in the US. This has prompted us and others to search for improved biomarkers for CaP, to facilitate early detection and disease stratification. In this regard, autoantibodies (AAbs) against tumor antigens could serve as potential candidates for diagnosis and prognosis of CaP. Towards this, our goals were: i) To investigate whether AAbs against ERG oncoprotein (overexpressed in 25-50% of Caucasian American and African American CaP) are present in the sera of CaP patients; ii) To evaluate an AAb panel to enhance CaP detection. The results using an enzyme-linked immunosorbent assay (ELISA) showed that anti-ERG AAbs are present in a significantly higher proportion in the sera of CaP patients compared to healthy controls (p = 0.0001). Furthermore, a panel of AAbs against ERG, AMACR and human endogenous retrovirus-K Gag successfully differentiated CaP patient sera from healthy controls (AUC = 0.791). These results demonstrate for the first time that anti-ERG AAbs are present in the sera of CaP patients. In addition, the data also suggest that AAbs against ERG together with AMACR and HERV-K Gag may be a useful panel of biomarkers for diagnosis and prognosis of CaP.

MAD2 Combined with Mitotic Spindle Apparatus (MSA) and Anticentromere Antibody (ACA) for Diagnosis of Small Cell Lung Cancer (SCLC)

“…A number of studies have shown that autoantibodies can have low titers in tumorigenesis. These autoantibodies, targeting carcinoma antigen, could have an effect on receptors of carcinoma cells, thereby stopping cell proliferation [21,22]. They come into being in the early stage of carcinoma.…”

Human Endogenous Retrovirus K (HML-2) in Health and Disease

“…In melanoma, anti-HERV-K Gag and Env antibodies were negatively related to disease-specific overall survival, suggesting that humoral anti-HERV-K immune response may provide additional prognostic information to that of established melanoma markers (Hahn et al, 2008). Autoantibodies against HERV-K Gag together with ERG and AMACR may be a useful panel of biomarkers for diagnosis and prognosis of prostate cancer (Rastogi et al, 2016). Anti-HERV-K antibodies were detected in patients with ovarian cancer, but not in normal female controls, documenting that HERV Env proteins, especially those expressed on the cell surface, may serve as novel tumor targets for detection, diagnosis, and immunotherapy of ovarian cancer (Wang-Johanning et al, 2007).…”

Human Endogenous Retrovirus K in Cancer: A Potential Biomarker and Immunotherapeutic Target

“…Both anti-HERV antibodies and HERV mRNA have been reported as biomarkers for prostate cancer and antibody production has been discussed as potential cancer immunotherapy [ 118 , 119 , 123 , 124 , 125 , 126 ]. HERV-K gag mRNA expression in prostate cells is regulated by both HERV promoter demethylation and androgen stimulation [ 117 ].…”

“…A panel for the detection of autoantibodies, including those against HERV and three host proteins, has been tested for analyzing the potential of using these autoantibodies in the diagnosis of prostate cancer [ 119 ]. The results showed that the detection of the anti HERV-K Gag antibody along with other host antibodies was successful in differentiating cancer patients from healthy subjects [ 119 ].…”

“…A panel for the detection of autoantibodies, including those against HERV and three host proteins, has been tested for analyzing the potential of using these autoantibodies in the diagnosis of prostate cancer [ 119 ]. The results showed that the detection of the anti HERV-K Gag antibody along with other host antibodies was successful in differentiating cancer patients from healthy subjects [ 119 ]. Furthermore, the anti-HERV-K Gag antibody is more frequent in serum from patients with advanced prostate cancer (stage III–IV) when compared to patients with early prostate cancer (stages I–II) [ 117 ].…”