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

Abstract

Abstract 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 SLC25A1 protein expression levels were further validated in a tissue microarray. 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 in cancers. In addition, the correlation between tumor-infiltrating immune cells and SLC25A1 varies across different cancer types. Furthermore, the knockoutof SLC25A1 demonstrated inhibitory effects in the majority of cell lines for all cancer types. Conclusions: Our findingssuggest the potential of SLC25A1 as a prognostic biomarker for cancers and a therapeutic target for precise antitumor strategy and cancer immunotherapy.