Prostate cancer-associated autoantibodies in serum against tumor-associated antigens as potential new biomarkers

Abstract

The limitations of the current prostate cancer (PCa) screening tests demands new biomarkers for early diagnosis of PCa. In this study, we aim to investigate serum autoantibody signatures as PCa specific biomarkers. PCa proteins were resolved by 2-DE and then transferred onto polyvinylidene difluoride membrane, which were subsequently incubated with either pooled serum from PCa patients or from normal controls. Mass spectrometry results have identified 18 antigens from 21 different 2-DE spots associated with PCa. Autoantibody response to antigens PRDX2, PRDX6 and ANXA11 in PCa patient's sera was confirmed using recombinant antigens. Further validation with an independent set of PCa patient's sera have shown relatively increased abundance of PRDX6 and ANXA11 antibodies in PCa patients. Formal concept analysis method was applied to assess whether the abundance of these autoantibodies could influence the classification of patients. However, sensitivity of the single antibody to discriminate prostate tumor and healthy controls varies from 70% to 80%, whereas combination of both PRDX6 and ANXA11 antibodies increased sensitivity to 90% for tumors and 100% for healthy controls. Therefore, we hereby report that the detection of these antibodies in PCa patient's serum in combination with the existing non-invasive diagnostic procedures may have significance in PCa diagnosis.

BIOLOGICAL SIGNIFICANCE:

The present study aimed to investigate serum autoantibody signatures as new biomarkers for early diagnosis of prostate cancer (PCa). To investigate serum autoantibodies in patients with PCa, we used proteomics approach based on two-dimensional gel electrophoresis (2-DE) and mass spectrometry. Total tissue proteins extracted from prostate were separated by 2-DE and then transferred onto polyvinylidene difluoride (PVDF) membrane, which were subsequently incubated with either pooled serum from PCa patients or from normal controls with no history for PCa. Proteomic analysis results have identified 18 antigens that showed antibody response specifically to cancer patient's serum. For validation experiments using recombinant antigens, confirmed autoantibody response to three antigens PRDX2, PRDX6 and ANXA11. Further validation using a second independent set of PCa patient's sera has shown relatively increased abundance of PRDX6 and ANXA11 antibodies specifically in PCa patients. Partition analysis of patients based on abundance of autoantibodies highlighted a combination of both PRDX6 and ANXA11 antibodies in serum with 90% sensitivity in case of tumors and 100% in case of healthy controls. Therefore, we hereby report that the detection of these antibodies in PCa patient's serum in combination with known markers may have significance in diagnosis of PCa with further validation in larger cohort of samples.