Expression, Prognostic and Immunological Roles of USP8 in kidney renal clear cell carcinoma: An Integrated Analysis

Abstract Background USP8 is a deubiquitinating enzymes (DUBs) that belongs to the ubiquitin-specific processing (USP) protease family. Previous study revealed that USP8 overexpressed and acted as oncogenes in multiple cancers. However, the function of USP8 in kidney renal clear cell carcinoma (KIRC) remains unclear. This research aimed to investigate USP8 expression, prognostic value and its possible roles in tumor immunity in KIRC. Methods Data on patients diagnosed with KIRC were extracted from the TCGA-KIRC and other public omics databases. We detected the expression profiles, clinical relevance and diagnostic value of USP8 in KIRC using GEPIA, UALCAN, GTEx, TIMER, Kaplan-Meier Plotter and HPA Database. The epigenetic characteristics of USP8 were detected by UALCAN and DNMIVD Database. Co-expressed with USP8 and related mechanism analyses were conducted by retrieving data in STRING and cBioPortal. In addition, immune infiltration, single-cell expression and immunotherapy-related analyses were performed by TIMER and TISCH2. Results Low expression levels of USP8 were observed in most cancer types. USP8 mRNA and proteins were downregulated in KIRC. Detection of epigenetics and genetics of USP8 suggested that its expression was negatively related to DNA methylation. Higher-expressed USP8 patients had a better prognosis, including overall survival (OS) and disease free survival (DFS). USP8 mRNA was aberrantly downregulated and correlated to sample types, tumor grade, stages, subtypes and nodal status. Immune infiltration and single-cell analysis suggested the indispensable role of USP8 expression in immune cell infiltration, indicating that USP8 may be an underlying predictor of immune treatment effects for KIRC patients. Meanwhile, the USP8-related gene expression signature in KIRC is correlated to the enrichment of genes involved in the ErbB signaling pathway, Ubiquitin mediated proteolysis, EGFR tyrosine kinase inhibitor resistance, etc. Conclusions Methylated USP8 may act as a novel prognostic and immunotherapy biomarker for KIRC.