Solute carrier family 16 member 5 downregulation and its methylation might serve as a prognostic indicator of prostate cancer

Abstract

Prostate cancer (PCa), characterized by high invasion, metastasis, and recurrence, is the most prevalent malignant tumor in men worldwide. A clear understanding of the underlying molecular mechanisms and their role during PCa tumorigenesis can help develop prognostic and targeted therapies. We analyzed datasets from public databases, including the Cancer Genome Atlas (TCGA) and Oncomine and Gene Expression Profiling Interactive Analysis for differential expression of solute carrier family 16 member 5 (SLC16A5). We further investigated its relationship with clinical stage, pathological grade, and prognosis of PCa. The promoter methylation level of SLC16A5 in PCa was also investigated by UALCAN. We also utilized datasets from UCSC Xena to explore the prognostic role of SLC16A5 methylation levels and CpG site. Correlations between SLC16A5 and immune infiltration were discovered through TIMER. We observed significantly lower levels of SLC16A5 mRNA in PCa relative to normal tissues across six datasets from Oncomine database (p < .001) and 498 cases from TCGA database (p < .0001). SLC16A5 is strongly negatively regulated by its DNA methylation, with a Spearman of -0.81 and Pearson of -0.80 (p < .001). The aberrant SLC16A5 expression resulted in a significant relationship with clinical stage, pathological grade, and lower SLC16A5 mRNA expression, and its hypermethylation was related to a poorer PCa prognosis. SLC16A5 acted as an important factor for PCa diagnosis, with an AUC of 0.9038 (95% CI: 0.8597-0.9479; p < .0001). Besides, the aberrant SLC16A5 expression revealed close correlations with multiple immune cells. Overall, these results indicate that decreased SLC16A5 expression might be a potential biomarker for determining prognosis and immune infiltration in PCa. The positive SLC16A5 modulation might be a promising therapeutic target for PCa.

Keywords: immune cell infiltration; methylation; prognosis; prostate cancer; solute carrier family 16 member 5 (SLC16A5).