Prostate cancer remains one of the most prevalent cancers detected in males; yet current detection methods still lack adequate specificity and sensitivity. While major improvements in screening have led to a reduction in advanced disease and mortality, patient overdiagnosis and overtreatment have in turn, become problematic. While most prostate tumours tend to be slow-growing and indolent, the high prevalence of the disease still results in a range of heterogenous clinical outcomes varying on a patient-by-patient basis. Many clinical, pathological, molecular and genetic factors have been explored for prognostic utility, but only few are routinely used. This emphasises the growing need for the discovery of novel diagnostic and prognostic biomarkers capable of effectively distinguishing healthy men and those with benign conditions from patients with prostate cancer, and effectively delineating indolent from aggressive disease.
In this study, we screened serum samples from a retrospective cohort of prostate cancer patients (n=110) using a customised cancer array (CT100+) containing 123 cancer antigens, generating discrete autoantibody profiles for each patient. Downstream analyses were conducted to assess the efficacy of discovered cancer-associated autoantibodies as diagnostic and prognostic biomarkers using clinicopathological data. Findings inferred that combinations of unique autoantibodies could be used to detect prostate cancer with high sensitivity and specificity and aid in the prediction of disease outcome (i.e. relapse and survival). We also conducted multiplex immunohistochemistry on prostatectomy tissue samples from a subset of these patients (n=64) in order to investigate correlations between antibody-secreting cells, tertiary lymphoid structures, and autoantibody profiles. Finally, our array-based diagnostic findings were validated using an additional external cohort of prostate cancer patients (n=99).
In conclusion, the incorporation of circulating autoantibodies with current prostate cancer screening procedures has the potential to substantially improve diagnostics and prognostics, thereby reducing overdiagnoses and enabling informed therapeutic interventions.