Abstract
At present, the overall genetic and epigenetic effects of Krüppel-like factors (KLFs) on prostate cancer (PCa) remain unclear. Therefore, we systematically investigated the molecular differences in KLFs of transcription expression, promoter methylation and genetic alteration. Univariate and multivariate Cox proportional hazard regression was used to analyse the effect on RFS and establish the prognostic signature in the TCGA cohort, MSKCC and GSE116918 cohorts employed to validate the signature. Biological pathway enrichment and the potential response to immunotherapy and chemotherapy were inferred. The transcription levels of most KLFs are associated with the clinical outcome of PCa. Gleason score (P = .009), pathology T stage (P = .006), KLF3 (P = .034), KLF5 (P = .002) and KLF7 (P = .035) were independent prognostic factors. A prognostic signature was established in the TCGA cohort (P < .001) and validated in the MSKCC (P < .001) and GSE116918 cohorts (P = .006). Demethylation of KLF5 by 5-azacytidine led to increased protein levels, whereas knockdown of KLF5 promoted cell proliferation. Patients in KLF-F were more likely to respond to immunotherapy (P < .001) and bicalutamide (P < .001). In summary, we found that the KLFs and clinical feature-based signatures may improve prognosis prediction in PCa and further promote patient stratification and disease management.