A Pan-Cancer Analysis of Deubiquitinating Enzyme Ubiquitin-Specific Protease 9X as a Prognostic and Immunological Biomarker in Human Tumors

Abstract

Background: USP9X (ubiquitin-specific protease 9X) is a substrate-specific deubiquitinating enzyme that regulates multiple components of diverse signaling pathways. The deregulation of USP9X is associated with various types of diseases. However, the role that USP9X plays in human pan-cancer remains largely unknown. Methods: A variety of bioinformatics methods were used to comprehensively analyze the expression level, survival relationship, mutation, protein phosphorylation, and immune infiltration of USP9X in various tumors from public databases. Results: USP9X was found to exhibit a dual role in different tumors. The expression of USP9X was high in tumors tissues of CHOL (cholangiocarcinoma), ESCA (esophageal carcinoma), HNSC (head and neck squamous cell carcinoma), and STAD (stomach adenocarcinoma), but low in tumors tissues of BLCA (bladder urothelial carcinoma), KIRC (kidney renal clear cell carcinoma), KIRP (kidney renal papillary cell carcinoma), PRAD (prostate adenocarcinoma), THCA (thyroid carcinoma), and UCEC (uterine corpus endometrial carcinoma). There is a differential association between the expression of USP9X and the prognosis of cancer patients. The level of phosphorylation was high or low at different sites in different tumors. Moreover, the expression of USP9X was associated with levels of immune infiltration of CAFs (cancer-associated fibroblast), B cells, neutrophil, CD8⁺ T cells, CD4⁺ T cells, Tregs, dendritic cells (DCs), as well as macrophages in most cancers. In particular, HNSC, HNSC-HPV (human papilloma virus)-, and PAAD (pancreatic adenocarcinoma) in CAFs and BLCA and THCA in neutrophils showed a significant positive correlation with USP9X expression in all algorithms. Conclusions: This is the first pan-cancer study on USP9X that summarizes the prognostic and immunological role of USP9X in different tumors.