Extensive serum cytokine analysis in patients with prostate cancer

Prostate cancer (CaP) is a common male malignancy. Using prostate specific antigen (PSA) and prostate cancer antigen 3 (PCA3) in the diagnosis of prostate cancer, sensitivity and specificity still require improvement. Additional targets are urgently needed for the diagnosis, prognosis, and prediction of therapeutic response, leading to better treatments in order to reduce the mortality of CaP. Here, we utilized a solid-phase antibody array, which can simultaneously detect 200 proteins, for the screening of novel blood-based biomarkers. The proteins differentially expressed in the pathogenesis of CaP were further analyzed using bioinformatics methods. The identified targets were further validated by the enzyme-linked immunosorbent assay (ELISA). A total of 38 proteins were identified with significantly differential levels in CaP serum compared to healthy control serum, including 21 up-regulated and 17 down-regulated cytokines. ELISA result showed that validated six ones of these differential cytokines were significantly differential between CaP and control, consistent with the antibody array result. The protein-protein interaction (PPI) analysis for these differentially expressed cytokines showed the top five cytokines interacting with most other cytokines were insulin, SDF-1a, CD40L, IL-18 and NCAM-1, suggesting these five targets are important in the pathogenesis of CaP, and more sensitive for the early diagnosis and prognosis of CaP. Targeting these cytokines may be more effective therapies against CaP. Among these differentially expressed cytokines, it was found that AR, BTC, IL-1 F8, IL-31, Marapsin, b-NGF, EDA-A2, MCP-3, MCP-4, MIP-3a, PIGF, and TECK decreased, while Fas, Flt-3L, and NCAM-1 increased in CaP when compared to the controls. Taken together, those 38 differentially expressed cytokines may service as novel serum biomarkers for CaP, which will be further validated with more clinical samples.