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.
Highlights
Prostate cancer (CaP) is a prevalent disease among US men and accounts for a total of an estimated 180,890 cases diagnosed in 2016 with 26,120 deaths [1]
This study aims to determine the following: i) Whether AAbs against ERG are present in the sera of CaP patients; ii) Whether a multiplex AAb panel containing ERG, AMACR, C-MYC, and human endogenous retrovirus-K (HERV-K) Gag improves the detection of CaP
It has been shown that the ERG 9FY mouse monoclonal antibody (MAb) and the Epitomics ERG rabbit MAb (# 5115) recognize epitopes located at the Nand C-terminal regions of the ERG protein, respectively [7, 69]
Summary
Prostate cancer (CaP) is a prevalent disease among US men and accounts for a total of an estimated 180,890 cases diagnosed in 2016 with 26,120 deaths [1]. Convincing evidence demonstrates that the PSA test often produces false-positive results: approximately 80% of positive results are false when using a cutoff between 2.5 and 4.0 μg/L [4] This leads to a substantial number of men which are over-diagnosed, resulting in over-treatment for CaP [5], the U.S Preventative Services Task Force recently recommended against PSA-based screening for CaP [6]. Prognostic assays that detect the expression of cellular genes using samples derived from needle biopsies or radical prostatectomy specimens are currently available, such as Prolaris (Myriad Genetics) [11], Oncotype DX® (Genomic Health) [12,13,14], and Decipher (Genome DX) These assays contribute to improved risk assessment, the overall cost is much higher. These findings make the case that AAbs could be used as potential biomarkers for early detection and as prognostic markers associated with progression of the disease
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