βKlotho Inhibits Cell Proliferation by Downregulating ELK4 and Predicts Favorable Prognosis in Prostate Cancer

Abstract

Objective: Prostate cancer (PCa) ranks as the second common malignancy in males world-wide. Although conspicuous progressions in diagnosis and treatment have been achieved in the past decades, the prognosis expectation of PCa remains unsatisfied yet. To improve the prognosis prediction of PCa, more specific biomarkers are needed. In this retrospective research, we focused on βKlotho and ETS-like transcription factor 4 (ELK4), aiming to identify potential prognostic biomarkers for PCa. Methods: Western blotting was used to determine the expression of βKlotho, ELK4, and PARP in C4-2B and PC3 PCa cell lines. CCK-8 assay and colony formation assay were applied to examine the roles of βKlotho and ELK4 in the proliferation of PCa cells. The expression of βKlotho and ELK4 in PCa tissue samples was determined by immunochem-istry. Pearson’s χ2 test and Fisher’s exact test were performed to investigate the associations among βKlotho, ELK4 and various clinical factors. Kaplan–Meier curves and Cox regression model were established to reveal the correlation among βKlotho, ELK4 expression and the prognosis of patients. Results: βKlotho overexpression down-regulated the ELK4 expression, induced apoptosis and inhibited cell proliferation in both C4-2B and PC3 cells, which were reversed by ELK4 overexpression. βKlotho expression in PCa tissue samples had negative correlation with the ELK4 expression, and higher βKlotho expression was associated with lower Gleason score, absent distant metastasis and lower prostate-specific antigen (PSA) level. On the contrast, higher ELK4 expression was correlated with distant metastasis and higher PSA level. Moreover, βKlotho and ELK4 were both recognized as independent factors for the prognosis of patients with PCa. Conclusion: βKlotho inhibits proliferation of prostate cancer cells by downregulating ELK4. Both βKlotho and ELK4 expressions correlate with the prognosis of PCa, which may serve as potential biomarkers for follow-up surveillance and prognostic assessments.