IRF1 expression might be a biomarker of CD8+ T cell infiltration in cutaneous melanoma

Abstract

ABSTRACT Objective This study aimed to explore the expression profile of interferon regulatory factor (IRF) genes in skin cutaneous melanoma (SKCM), their association with CD8 + T cell infiltration, and the potential regulatory network in melanoma and non-melanoma cells. Methods Bioinformatic analysis was conducted using the SKCM subset of The Cancer Genome Atlas (TCGA) Pan-Cancer, Genotype-Tissue Expression Project (GTEx), and single-cell RNA-seq data from the Human Protein Atlas and Jerby-Arnon et al. 2018ʹs dataset. Results IRF1 expression is robustly associated with moderate to strong CD8 + T cell infiltration in the tumor microenvironment. It is ubiquitously expressed in tumor and non-tumor cells in melanoma. Melanoma tumor cells and macrophages had 16/36 and 9/27 cell-specific IRF1-correlated genes, respectively. The methylation of four CpG sites (cg00255919, cg21138405, cg15375424, and cg27587780) within the IRF1 gene locus showed moderate to strong negative correlations with IRF1 expression. Conclusion IRF1 expression might serve as a biomarker indicating CD8 + T cell infiltration in skin melanoma. It might exert different regulatory effects in melanoma and non-melanoma cells in the tumor microenvironment. Cg00255919, cg21138405, cg15375424, and cg27587780 are four critical CpG sites that might modulate the transcription of IRF1.