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

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.

KEYWORDS:

• CD8+ T cells
• IRF1
• cutaneous melanoma
• tumor microenvironment

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

S Zhou: Conceptualization; data curation; formal analysis; investigation; methodology; validation; writing-original draft; writing-review and editing; G Liu: data curation; visualization; writing-original draft. C Lu: investigation; resources. Q Hu: conceptualization; data curation; formal analysis; writing-review and editing. J Yang: supervision; writing-review and editing. All authors read and approved the final manuscript for publication.

Ethical approval statement

The data used for bioinformatic analysis in this study were from online open databases, in which the data are anonymous. No primary patient data were collected by any author in the current study. Therefore, ethical approval is not required.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/1744666X.2022.2141228

Additional information

Funding

This paper was not funded.