Comprehensive prognostic and immunological analysis of Ubiquitin Specific Peptidase 28 in pan-cancers and identification of its role in hepatocellular carcinoma cell lines

Background: Ubiquitin Specific Peptidase 28 (USP28), as a member of the DUBs family, has been reported to regulate the occurrence and development of some tumors, but its oncogenic role in tumor immunity is still unknown. Methods: The comprehensive view of USP28 expression in tumor and normal samples was obtained from public databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE). We analyzed the genomic alterations of USP28 in various cancers using the cBioPortal dataset. Besides, gene set enrichment analysis was used to analyze the associated cancer hallmarks with USP28 expression, and TIMER2.0 was taken to investigate the immune cell infiltrations related to the USP28 level. Results: USP28 is highly expressed in most tumors and has prognostic value across various cancer types. Moreover, a significant correlation exists between USP28 and immune regulators, clinical staging, checkpoint inhibitor response, MSI, TMB, CNV, MMR defects, and DNA methylation. Additionally, USP28 expression is strongly associated with the infiltration levels of neutrophils and NK cells in most tumor types. One of the most significant findings of our study was that USP28 could serve as a significant predictor of anti-CTLA4 therapy response in melanoma patients. Additionally, our molecular biology experiments validated that the knockdown of USP28 substantially reduced the proliferative and invasive abilities of the HCC cell lines. Conclusions: Our study suggests that USP28 could potentially serve as a biomarker for cancer immunologic infiltration and poor prognosis, with potential applications in developing novel cancer treatment strategies.