USP21 stabilizes immune checkpoint of CD276 and serves as an immunological and tumor prognostic biomarker

Ubiquitin-specific protease 21 (USP21) belongs to the ubiquitin-specific protease family and is a member of the deubiquitinating enzyme (DUB) family. Previous research has shown that USP21 promotes cancer initiation and progression. However, there have been few pan-cancer analysis on USP21. We analyzed the expression levels of USP21 mRNA and protein in various human tumor tissues using several public databases such as The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and Human Protein Atlas (HPA). Kaplan-Meier survival analyses were utilized to test the effect of USP21 on overall survival (OS) and progression-free interval (PFS) of these tumor patients. Our study demonstrated that USP21 was differentially expressed between normal and malignant tissues, conferring a notable value in evaluation of prognosis and diagnosis. In addition, enrichment and correlation analyses linking USP21 with immune features such as immune-cell-infiltration rate and immune-checkpoint-gene expression indicated that USP21 is an applicable immunotherapeutic marker for liver cancer. To further elucidate the role of USP21, we downregulated its expression in hepatocellular carcinoma cells and identified a remarkable decrease in expression of the immune checkpoint CD276, which contributes to the immune escape of tumor cells by suppressing the immune system. Together, our results indicated a promising potential of USP21 for future tumor prevention.