IMR Press / FBL / Volume 27 / Issue 6 / DOI: 10.31083/j.fbl2706190
Open Access Original Research
Gene Signature and Prognostic Value of Ubiquitin-Specific Proteases Members in Hepatocellular Carcinoma and Explored the Immunological Role of USP36
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1 Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, 230022 Hefei, Anhui, China
2 Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021 Beijing, China
*Correspondence: (Yufeng Gao); (Leilei Liang)
These authors contributed equally.
Academic Editor: Cheng-Maw Ho
Front. Biosci. (Landmark Ed) 2022, 27(6), 190;
Submitted: 29 March 2022 | Revised: 6 May 2022 | Accepted: 26 May 2022 | Published: 15 June 2022
(This article belongs to the Special Issue Cutting Edge Research in Hepatocellular Carcinoma)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Ubiquitination is one of the most common post-translational modifications in cells and dysregulation is closely associated with the development of cancer. However, a comprehensive analysis of the role of ubiquitination in hepatocellular carcinoma (HCC) is still lacking. In this study we analyzed expression and prognostic value of Ubiquitin-Specific Proteases (USPs) in HCC, and the immunological role of USP36 in HCC. Methods: Expression data, prognostic data, and DNA methylation data in cases of HCC were obtained from the cancer genome atlas (TCGA). Overexpression of USP36 in HCC was confirmed in the gene expression omnibus (GEO) database and verified by quantitative PCR in 10 pairs of HCC samples. ULCAN was used to analyze the correlation between USP36 and clinicopathological features. TIMER2.0 and DriverDBv3 were used to analyze the USP36 mutational profile. GSEA analysis explored the potential signaling pathways of USP36 affecting HCC. The immune and stromal scores of HCC samples were calculated using the ESTIMATE algorithm. TIMER1.0 was used to explore the correlation between USP36 and immune cell infiltration. Finally, we analyzed the correlation of USP36 expression with immune checkpoint molecules and determined the IC50 values of 6 chemotherapeutic drugs using the pRRophetic software package. Results: Most USPs are abnormally expressed in HCC, among which USP36 and USP39 are most closely associated with HCC prognosis. We also found that USP36 is associated with TP53 mutational status. GSEA analysis indicated that USP36 may affect HCC progression through the dysregulation of various pathways such as ubiquitin-mediated proteolysis. USP36 expression positively correlated with both macrophage infiltration levels and multiple immune checkpoint molecules. Finally, chemosensitivity analysis indicated that chemosensitivity was lower in cells within the USP36 high expression group. Conclusions: Most USPs are abnormally expressed in HCC. Overexpression of USP36 in HCC is closely related to poor prognosis. In particular, the unique immunological role of USP36 may have potential clinical application value.

Ubiquitin-Specific Proteases (USPs)
bioinformatics analysis
Fig. 1.
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