A comprehensive analysis of SLC25A1 expression and its oncogenic role in pan-cancer

Objective The solute carrier family 25 member 1 (SLC25A1) is currently the only known human transporter for citrate in the mitochondrial membrane. However, its role in cancer development remains to be elucidated. We aim to analyze the expression profile, prognostic value, potential immunological significance, and effect on tumor growth of SLC25A1 at a pan-cancer level. Methods Herein, the role of SLC25A1 in tumorigenesis and progression was investigated based on the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), Clinical Proteomic Tumor Analysis Consortium (CPTAC), GeneMANIA, STRING and Cancer Dependency Map Project (DepMap) database via online websites or the R software. The protein expression levels were validated in tissue microarrays, and the effects on tumor cell lines were accessed through MTS and colony formation assays. Results The expression of SLC25A1 increased in most cancers, and the upregulation of SLC25A1 in colon adenocarcinoma and lung adenocarcinoma was further confirmed by immunohistochemistry. Meanwhile, SLC25A1 was linked to clinical outcomes across multiple tumor types, particularly in lung adenocarcinoma, where its high expression predicted poor prognosis. Moreover, SLC25A1 was positively associated with MSI, TMB, and CD276 and tightly correlated with tumor-infiltrating immune cells. Furthermore, the knockout of SLC25A1 demonstrated inhibitory effects in most cancer cell lines in the DepMap project. Cellular experiments showed that SLC25A1 knockdown significantly reduced the proliferation of lung adenocarcinoma cells. Conclusions Our findings suggest the potential of SLC25A1 as a prognostic biomarker for cancers and a therapeutic target for precise antitumor strategy and cancer immunotherapy.