Downregulation of SFRP1 in Enzalutamide-Resistance Prostate Cancer is Associated with Angiogenesis and Regulatory T Cell Infiltration.

BACKGROUND

While enzalutamide has demonstrated reliable therapeutic efficacy in the management of prostate cancer (PC), a substantial proportion of patients eventually develop resistance to this medication after prolonged therapy. Despite this, the identification of biomarkers to effectively predict clinical outcomes in PC patients who exhibit resistance to enzalutamide remains uncertain. The aim of this study was to identify a specific gene associated with acquired resistance to enzalutamide in PC and to investigate the potential prognostic value of this gene.

METHODS

The GSE183100, GSE147541, and GSE16560 datasets were obtained from the Gene Expression Omnibus database. Differential gene expression analysis was conducted using the DESeq2 R package and Wilcoxon's rank-sum test. Subsequently, biological process enrichment analysis and gene set variation analysis were performed to identify a promising candidate gene. Additionally, the correlation between the proportions of immune cell infiltration and the expression of candidate genes was evaluated. Finally, the potential implications of these candidate genes on survival outcomes were investigated.

RESULTS

A comprehensive analysis identified a total of 975 differentially expressed genes, predominantly involved in biological processes related to angiogenesis, inflammatory response, positive regulation of cell division, and membrane potential. Notably, secreted frizzled-related protein 1 (SFRP1) expression demonstrated strong, favorable correlations with both angiogenesis and the infiltration of Regulatory T cells. Moreover, the overexpression of SFRP1 was found to be closely associated with improved prognosis in patients with PC.

CONCLUSIONS

In conclusion, the downregulation of SFRP1 in enzalutamide-resistance PC is associated with angiogenesis and cellular infiltration. This study identified SFRP1 as a diagnostic biomarker for patients with PC who have developed acquired enzalutamide resistance. These findings provide an important theoretical foundation for the development of novel and complementary therapeutic approaches for PC management.