SLC15A2 Serves as a Novel Prognostic Biomarker and Target for Prostate Cancer.

Abstract

Background/aim: Solute carrier (SLC) family 15 member 2 (SLC15A2) is an integral member of the SLC family that plays a pivotal role in numerous biological processes, including the regulation of cellular signaling pathways. However, its role in prostate cancer (PCa) remains inadequately elucidated. This study aims to investigate the prognostic significance of SLC15A2 in PCa.

Materials and methods: We evaluated the expression levels and prognostic significance of SLC15A2 in multicenter cohorts of PCa through differential expression analysis, survival analysis, and Cox regression. These findings were validated through immunohistochemistry and in vitro experiments. Gene set enrichment analysis, mutation analysis, and methylation analysis were used to investigate the potential biological functions of SLC15A2. Finally, drug target prediction analysis was conducted to identify small molecule therapeutic agents specifically targeting SLC15A2 in PCa.

Results: The expression level of SLC15A2 in PCa tissues was significantly lower compared to benign tissues, and reduced expression of SLC15A2 was often associated with early biochemical recurrence (BCR) and decreased overall survival in PCa patients. Moreover, results from in vitro experiments indicated that knockdown of SLC15A2 markedly enhanced the proliferation and migratory capacity of PCa cells. Enrichment analysis indicated that SLC15A2 predominantly activates pathways related to cell proliferation, adhesion, and lipid metabolism while inhibiting pathways associated with protein synthesis, degradation, RNA metabolism, and energy metabolism. Notably, the frequency of TP53 mutations and 8q24.21 copy number variations was significantly higher in the low SLC15A2 expression group. DNA hypermethylation of SLC15A2 at gene body linked to downregulation of SLC15A2 in PCa. Finally, analysis with the Connectivity Map database identified several promising small molecule drugs for PCa treatment, including rucaparib.

Conclusion: Our findings suggest that SLC15A2 serves as a promising prognostic biomarker in PCa, enabling accurate risk stratification for BCR. This insight may contribute to the advancement of personalized treatment strategies for PCa.