Abstract
BACKGROUND: Solute carrier family 12 member 7 (SLC12A7) is a membrane transporter implicated in ion homeostasis. Recent studies have suggested its aberrant expression in various malignancies; however, its functional roles and clinical relevance across cancers remain poorly defined. Given the limited understanding of SLC12A7 in oncogenesis and the urgent need for novel biomarkers, particularly in hepatocellular carcinoma (HCC), we conducted a comprehensive pan-cancer analysis to elucidate its potential oncogenic roles. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), cBioPortal, TIMER 2.0, and Gene Expression Omnibus (GEO) were integrated to investigate the expression patterns, prognostic significance, genetic alterations, and immune correlations of SLC12A7. Single-cell RNA sequencing data were analyzed to examine its heterogeneity within the tumor microenvironment. Functional enrichment analyses were performed to identify associated signaling pathways. In vitro experiments were conducted to validate the effects of SLC12A7 on proliferation, migration, and invasion in HCC cell lines. RESULTS: SLC12A7 was significantly upregulated in multiple cancer types and correlated with unfavorable clinical outcomes. Single-cell analysis revealed its enrichment in malignant cell populations and its involvement in the regulation of the tumor microenvironment. SLC12A7 expression was associated with immune cell infiltration and immune checkpoint gene expression. Functional assays confirmed that SLC12A7 enhances HCC cell proliferation, migration, and invasion. CONCLUSIONS: These findings identify SLC12A7 as a potential prognostic biomarker and immunotherapeutic target across cancers. Its oncogenic role in HCC suggests clinical utility in guiding prognosis and treatment strategies.