Decoding the Oncogenic Role of USP22 Through Pan‐Cancer Genomic and Epigenetic Analysis

BACKGROUND: Ubiquitin-specific protease 22, an important catalytic component of the human SAGA (Spt-Ada-GcN5 Acetyltransferase) complex, regulates the deubiquitination and methylation of histones, which in turn influences gene expression. Its overexpression alters gene regulation, transcription, cancer progression, and therapy resistance. Its role is increasingly being noticed in cancers. AIMS: To conducted a pan-cancer analysis across multiple malignancies, as it allows for a comprehensive assessment of USP22 expression, regulation, and clinical impact. METHODS: The Human Protein Atlas, UALCAN, and Timer 2.0 were used to examine USP22 expression at the gene and protein levels in 33 TCGA cancer types. Furthermore, various tools have been employed to study genetic changes, overall survival (OS), disease-free survival (DFS), DNA methylation profiles, and immune associations. Gene correlation and protein-protein interaction were examined. RESULTS: USP22 expression level was observed to be significantly higher in 13 distinct cancer types among the 33 TCGA cancer types. Along with the pathological stages of the TCGA sample, it showed overexpression in the histological subtypes, TP53 mutant stages, and tumor grade in numerous cancers compared to the control. According to the study, elevated USP22 expression was linked to a worse chance of survival and a lower OS rate in several types of cancer. High expression of USP22 is linked to a poor immunosuppressive microenvironment, and the CpG-aggregated methylation analysis shows that the gene is significantly hypomethylated in tumor samples, which is highly associated with its known upregulation in cancer. CONCLUSION: USP22 may have potential relevance in cancer, and the pathways associated with it could offer possible targets for therapeutic intervention.