Identification and validation of SLC16A8 as a prognostic biomarker in clear cell renal cell carcinoma: a six-gene solute carrier signature

Solute carrier (SLC) proteins are essential for nutrient transport, influencing tumor metabolism and growth while preserving cellular homeostasis. Despite the critical biological functions of these transporters, their applicability as therapeutic targets in clear cell renal cell carcinoma (ccRCC) remains largely unexplored. In the current study, we analyzed transcriptomic data and discovered 77 differentially expressed SLC genes in ccRCC, with 24 demonstrating predictive potential. Using Lasso regression, we developed a prognostic signature comprising six key genes: SLC2A3, SLC11A1, SLC14A1, SLC16A8, SLC22A6, and SLC28A1. This signature demonstrated strong diagnostic performance and served as an independent predictor of patient survival. Further analysis integrating clinical variables and risk scores enabled the construction of nomograms, which exhibited high predictive accuracy for patient outcomes. Immune profiling revealed distinct infiltration patterns between risk groups: high-risk patients showed elevated levels of memory B cells, activated CD4⁺ T cells, regulatory T cells (Tregs), M0 macrophages, and neutrophils. In contrast, their low-risk counterparts showed M1 macrophages, resting dendritic cells, and resting mast cells. Validation experiments confirmed that SLC16A8 was significantly overexpressed in ccRCC tissues compared to normal samples, correlating with poor prognosis. Functional studies demonstrated that SLC16A8 knockdown impaired tumor progression in vitro. Consistent with these findings, in vivo experiments demonstrated reduced tumor growth upon SLC16A8 knockdown. Mechanistically, decreased SLC16A8 attenuated PI3K/AKT signaling, suggesting a potential regulatory pathway in ccRCC progression. In summary, we established a six-gene SLC signature with significant prognostic value in ccRCC. Among these genes, SLC16A8 emerged as a promising biomarker and therapeutic target, warranting further investigation.