is a Potential Immunosuppressive Factor in Skin Cutaneous Melanoma

Background: As one of the most immunogenic malignancies, skin cutaneous melanoma (SKCM) is mainly characterized by a high prevalence in immune-compromised patients and a brisk lymphocyte infiltration in the tumor microenvironment (TME). However, to date, studies on deubiquitination in SKCM are still very limited.

Methods: Public data with regard to this study in SKCM patients were acquired from The Cancer Genome Atlas (TCGA) and the Gene-Expression Omnibus (GEO) databases. We stratified TCGA-SKCM cases using consensus clustering and identified independent prognostic factors in deubiquitinating enzymes encoding genes (DECGs) by LASSO-Cox analysis. transcriptome level was examined using public data and validated by Immunohistochemical (IHC) staining at the protein level. Enrichment analysis was used to explore the potential functions of , and the TISCH database, providing further evidence at the single-cell level. The CIBERSORT algorithm was used to assess the relationship between and the immune microenvironment, and IHC was used to further evaluate the relationship between USP35 and immunotherapy response. Finally, we used the cBioPortal and the Methsurv database to analyze the significance of genomic alterations of in melanoma.

Results: Our results showed that DECGs can be effectively used to stratify SKCM patients, suggesting their potential significance in the development of SKCM. Furthermore, overexpression was significantly associated with an unfavorable prognosis. We further revealed that may be involved in the activation of TORC1 signaling. Most importantly, was found to be significantly associated with an immunosuppressive TME, both in terms of negative correlation with the abundance of infiltrating CD8+ T cells and in terms of the fact that patients with high expression may benefit less from immunotherapy than those with low expression.

Conclusion: Deubiquitinating enzymes are of great importance in the diagnosis and treatment of SKCM, and is an extremely promising target for immunotherapy.