LAUSR

Simple Summary FBXO45 plays a role in the regulation of apoptosis through the ubiquitylation and degradation of specific target proteins. While FBXO45 has been suggested to have prognostic potential in various cancers, its specific role in prostate carcinoma (PCA) remains unclear. Transcriptome data concerning FBXO45 were analysed using The Cancer Genome Atlas (TCGA) and a publicly available Gene Expression Omnibus (GEO) progression PCA cohort. In addition, FBXO45 protein expression was evaluated using immunohistochemistry in a large cohort of PCA tissue microarrays. It was demonstrated that high FBXO45 expression was associated with advanced stages of PCA and biochemical recurrence. Shortened progression-free survival was associated with strong FBX045 staining, especially in TMPRSS2–ERG-positive PCA. In vitro experiments demonstrated that FBXO45 knockdown led to a significant reduction in migration capacity in the PC-3, DU-145 and LNCaP cell lines. These findings suggest that FBXO45 may serve as a promising biomarker for PCA and exhibit oncogenic properties. Abstract Background: F-box/SPRY domain-containing protein 1 (FBXO45) plays a crucial role in the regulation of apoptosis via the ubiquitylation and degradation of specific targets. Recent studies indicate the prognostic potential of FBXO45 in several cancers. However, its specific role in prostate carcinoma remains unclear. Methods: A systematic analysis of FBXO45 mRNA expression in PCA was performed using The Cancer Genome Atlas database and a publicly available Gene Expression Omnibus progression PCA cohort. Subsequently, FBXO45 protein expression was assessed via immunohistochemical analysis of a comprehensive tissue microarray cohort. The expression data were correlated with the clinicopathological parameters and biochemical-free survival. The immunohistochemical analyses were stratified according to the TMPRSS2–ERG rearrangement status. To assess the impact of FBXO45 knockdown on the tumour proliferation capacity of cells and metastatic potential, transfection with antisense-oligonucleotides was conducted within a cell culture model. Results: FBXO45 mRNA expression was associated with adverse clinicopathological parameters in the TCGA cohort and was enhanced throughout progression to distant metastasis. FBXO45 was associated with shortened biochemical-free survival, which was pronounced for the TMPRSS2–ERG-positive tumours. In vitro, FBXO45 knockdown led to a significant reduction in migration capacity in the PC3, DU145 and LNCaP cell cultures. Conclusions: Comprehensive expression analysis and functional data suggest FBXO45 as a prognostic biomarker in PCA.