Therapeutic and clinico-biological significance of CREB3L4 expression in primary prostate cancer

Purpose: To investigate the therapeutic, clinicopathological and biological relevancy of CREB3L4 expression in primary prostate cancer (PCa) and to determine the mechanisms underlying the deregulation of CREB3L4 expression in PCa. Methods: The therapeutic, clinicopathological and biological significance of CREB3L4 expressions in two cohorts of PCa, and the mechanisms of deregulation of CREB3L4 expression using TCGA data were determined using integrative computational analyses of the clinico-genomic data of the cancer genome atlas (TCGA) and Deutsches Krebsforschungszentrum (DFKZ). Result: Gene set enrichment analyses (GSEA) demonstrated enrichment of gene sets that predict biological responses to a range of approved inhibitors in the PCa subsets with low CREB3L4 expression, and at nominal and false discovery rates of p < 0.05 and p < 0.25, respectively. In addition, lower CREB3L4 expression in TCGA PCa cohort showed poorer outcomes following androgen deprivation therapy. Furthermore, GSEA demonstrated that cell proliferation, epithelial-mesenchymal transition, angiogenesis, inflammatory response and apoptosis gene sets were enriched in PCa subsets with low CREB3L4 expressions. Low CREB3L4 expression was associated with adverse clinicopathological features of PCa at adjusted p < 0.05. Multiple regression analysis of the methylation, microRNA expression and copy number data of CREB3L4 identified the methylation loci and miRNA expression which independently predicted the expression of CREB3L4 in PCa. Conclusion: This study demonstrates the potential therapeutic relevance and clinico-biological significance of CREB3L4 expression in primary PCa.