USP35 is a Potential Immunosuppressive Factor in Skin Cutaneous Melanoma

Qian Zhang,1,2,* Yuan-Jie Liu,1,2,* Jie-Pin Li,1– 3 Shu-Hong Zeng,1,2 Hui Shen,3 Mei Han,1 Shun Guo,1,2 Shen-Lin Liu,1,2 Xi Zou1,2,4 1Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China; 2No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 3Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, People’s Republic of China; 4Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xi Zou; Shun Guo, Email zxvery@126.com; retinoid@163.comBackground: 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. USP35 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 USP35, and the TISCH database, providing further evidence at the single-cell level. The CIBERSORT algorithm was used to assess the relationship between USP35 and the immune microenvironment, and IHC was used to further evaluate the relationship between USP35 and immunotherapy respons