ABCF2 is a prognostic and immunological pan-cancer biomarker with growth-promoting function in breast cancer: a multi-omics study

Background Unlike canonical members of the ABC transporter superfamily, ATP-binding cassette sub-family F member 2 (ABCF2) carries no transmembrane domains and participates in translational regulation. Nevertheless, its expression pattern, prognostic importance, genetic and epigenetic control, and immune-related effects have not been systematically evaluated across human malignancies, and its biological role and druggability in breast cancer remain unclear. We therefore combined multi-platform public omics data with in vitro and in vivo experiments to delineate the pan-cancer molecular features of ABCF2 and its impact on breast cancer malignant phenotypes. Methods TCGA and GTEx transcriptomic and clinical data were combined to evaluate ABCF2 expression, diagnostic value, and prognostic relevance (OS, DSS, and PFI) across 33 cancer types; CPTAC and HPA data served for protein-level validation. Genetic alterations, promoter methylation, m6A regulator associations, genomic heterogeneity indicators (TMB, MSI, NEO, MATH, HRD, and LOH), immune infiltration (ESTIMATE, ssGSEA, and TIMER-based deconvolution), functional enrichment (GO, KEGG, and GSEA), and drug sensitivity (CTRP and GDSC) were analyzed, and prognostic nomograms were built and validated. In BRCA, 16 paired clinical tissues and cell lines served to verify ABCF2 expression, and loss- and gain-of-function experiments (CCK-8, colony formation, wound healing, Transwell) plus a subcutaneous xenograft model defined its biological role. Results Most TCGA cancer types showed significant ABCF2 upregulation, and combined TCGA-GTEx analysis confirmed broad overexpression concordant at the protein level. High ABCF2 expression indicated poor OS in BRCA, GBM, LGG, LIHC, LUAD, and SKCM, acted as an independent prognostic factor in multiple cancers, and supported nomograms with modest-to-moderate discrimination; diagnostic accuracy exceeded an AUC of 0.9 in CHOL, COAD, LIHC, STAD, and THYM. ABCF2 overexpression was accompanied by gene amplification, promoter hypomethylation, and positive correlations with m6A regulators. Elevated ABCF2 coincided with an immunosuppressive milieu (less CD8+ T-cell infiltration, more Th2 cells and MDSCs, positive correlations with NECTIN2 and TGFB1). ABCF2-associated genes centered on ribosome biogenesis, DNA replication, and cell cycle, while high ABCF2 levels were associated with higher in silico IC50 estimates of several EGFR-targeted agents. In BRCA, silencing ABCF2 weakened malignant phenotypes in vitro and slowed xenograft growth in vivo , while overexpression produced the converse effects. Conclusion ABCF2 is frequently upregulated across cancer types and is associated with prognostic, diagnostic, and immune-related features; functional experiments support a growth-promoting role in breast cancer and nominate it as a candidate for further translational investigation.