The Role of Interleukin-6 and Interleukin-6 Receptor as Prognostic Biomarkers in Prostate Cancer

Background: IL-6 is known to play important roles in the growth of prostate cancer cells, activation of the androgen receptor and prostate-specific protein expression. It is reported that IL-6 promotes the growth of prostate cancer. Prostate Specific Antigen (PSA) does not directly assess the biological behavior of individual hormone-refractory prostate cancers, whereas serum biomarkers produced by tumors may correlate with disease progression. Prostate cancer cells, especially those that are hormone-refractory, secrete IL-6. We therefore evaluated the potential of circulating IL-6 levels as a marker of disease progression. Furthermore, we investigated the correlation with the expression of IL-6 receptor (IL-6R) and the effects of hormonal therapy against prostate cancer. Methods: We separated 21 patients with hormonal refractory prostate cancer into one group with more (higher group; n=9), and another with less (lower group; n=12) serum IL-6 than average. The correlation between prognosis and serum IL-6 level was investigated in these groups. Furthermore, in 57 specimens from patients with prostate cancer and benign prostatic hypertrophy, the expression of IL-6R was examined using immunohistochemistry. The correlation with immunoreactivity of IL6R and Gleason grade as well as histological effects of hormonal therapy was compared using the nonparametric Mann-Whitney U-test and generalized Wilcoxon test. Results: A comparison of disease-specific survival after PSA failure between these groups demonstrated that serum PSA and serum IL-6 levels were significantly correlated. The median survival after PSA failure was significantly shorter in the higher group than in the lower group (p=0.004). There were significant differences in IL-6R expression between medium Gleason grade and high Gleason grade (p=0.008), and BPH and high Gleason grade (p=0.004). Furthermore, the level of IL-6R expression was correlated with the histological effects of hormonal therapy against prostate cancer. Conclusion: The serum IL-6 level may be associated with the prognosis of patients with prostate cancer, and both IL-6 and PSA levels may indicate patients with a poor prognosis. In prostate cancer patients with strong expression of IL-6R, other therapeutic options without hormonal therapy, irradiation and/or chemotherapy should be chosen first. The expression of IL-6R may be helpful in predicting the effects of hormonal therapy against prostate cancer.