Background: Allograft Inflammatory Factor 1 (AIF-1) is a member of the allograft inflammatory factor gene family and plays an essential role in the occurrence and development of malignant tumors. However, little is known about the expression pattern, predictive value, and biological function of AIF-1 across cancers.

Materials and Methods: We first analyzed AIF-1 expression across cancers based on data from public databases. Univariate Cox regression and Kaplan-Meier analyses were used to explore the predictive value of AIF-1 expression in various cancers. Moreover, gene set enrichment analysis (GSEA) was applied to determine the cancer hallmarks associated with AIF-1 expression. Spearman correlation analysis was performed to investigate the association between AIF-1 expression and tumor microenvironment scores, immune cell infiltration, immune-related genes, TMB, MSI, and DNA methyltransferases.

Results: AIF-1 expression was upregulated in most cancer types and exhibited prognosis-predictive ability. AIF-1 expression was positively correlated with immune infiltrating cells and immune checkpoint-related genes in most cancers. Additionally, the promoter methylation level of AIF-1 was different in distinct tumors. High methylation levels of AIF-1 were associated with a worse prognosis in UCEC and melanoma, whereas they were associated with a better prognosis in GBM, KIRC, OV, and UVM. Finally, we found that AIF-1 was significantly highly expressed in KIRC tissues. Functionally, silencing AIF-1 dramatically decreased proliferation, migration, and invasion abilities.

Conclusion: Our results reveal that AIF-1 acts as a robust tumor biomarker and is closely correlated with tumor immune infiltration. Furthermore, AIF-1 may function as an oncogene and promote tumor progression in KIRC.