Differential expression of MCM2 and SKP2 as biomarkers of therapy resistance in prostate cancer

Abstract

Abstract Background Prostate cancer (PCa) is the second most incident cancer and the sixth cause of cancer death among man worldwide. Patients diagnosed with advanced PCa are often treated with androgen deprivation therapy. Although tumors initially respond, they may progress to a lethal and drug-resistant form of PCa. Recent works from our team demonstrated that a promising anti-cancer agent is associated with reduced MCM2 and SKP2 expression in PCa cell lines. MCM2 and SKP2 play an important role in cell cycle progression with overexpression observed in several cancers with association with poor prognostic. Thus, to test its potential as predictive biomarker, MCM2 and SKP2 expression was evaluated in PCa tissues. Methods A total of 57 cases (25 resistant and 33 non-resistant) were used to explore MCM2 and SKP2 expression by immunohistochemistry. Percentage of positive tumor cells, intensity of immunostaining, and immunoexpression were blinded evaluated. Comparisons between therapy conditions and proteins expression were assessed by Chi square test (statistical significance considered when P < 0.05). Results MCM2 expression is associated to PCa patients’ therapy resistance, with significant differences found for percentage of positive tumor cells (P = 0.001) and immunostaining intensity (P = 0.002). SKP2 expression is also associated with resistance to therapy, with differences observed referred to immunostaining intensity (P = 0.001) and immunoexpression pattern (P = 0.02). Specifically, cytoplasmatic and nuclear expression was apparent in most cases that developed therapy-resistance, whereas responsive PCa patients showed only SKP2 cytoplasmatic expression. Conclusions In PCa patients, MCM2 and SKP2 expression is significantly associated with therapy resistance. SKP2 cellular localization is also indicative of patients’ resistance to treatment.