Gene Signature and Prognostic Value of Ubiquitin-Specific Proteases Members in Hepatocellular Carcinoma and Explored the Immunological Role of USP36
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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
IMR Press
2022-06-01
|
| Series: | Frontiers in Bioscience-Landmark |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/FBL/27/6/10.31083/j.fbl2706190 |
| _version_ | 1811342790374719488 |
|---|---|
| author | Weijie Sun Jiapei Shen Jiaying Liu Kexing Han Leilei Liang Yufeng Gao |
| author_facet | Weijie Sun Jiapei Shen Jiaying Liu Kexing Han Leilei Liang Yufeng Gao |
| author_sort | Weijie Sun |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T19:17:13Z |
| format | Article |
| id | doaj.art-c8935aa17d92409386b0d0c047ddead3 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-04-13T19:17:13Z |
| publishDate | 2022-06-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-c8935aa17d92409386b0d0c047ddead32022-12-22T02:33:38ZengIMR PressFrontiers in Bioscience-Landmark2768-67012022-06-0127619010.31083/j.fbl2706190S2768-6701(22)00555-XGene Signature and Prognostic Value of Ubiquitin-Specific Proteases Members in Hepatocellular Carcinoma and Explored the Immunological Role of USP36Weijie Sun0Jiapei Shen1Jiaying Liu2Kexing Han3Leilei Liang4Yufeng Gao5Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, 230022 Hefei, Anhui, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, 230022 Hefei, Anhui, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, 230022 Hefei, Anhui, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, 230022 Hefei, Anhui, ChinaDepartment 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, ChinaDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, 230022 Hefei, Anhui, ChinaBackground: 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.https://www.imrpress.com/journal/FBL/27/6/10.31083/j.fbl2706190ubiquitin-specific proteases (usps)usp36hccimmunebioinformatics analysis |
| spellingShingle | Weijie Sun Jiapei Shen Jiaying Liu Kexing Han Leilei Liang Yufeng Gao Gene Signature and Prognostic Value of Ubiquitin-Specific Proteases Members in Hepatocellular Carcinoma and Explored the Immunological Role of USP36 Frontiers in Bioscience-Landmark ubiquitin-specific proteases (usps) usp36 hcc immune bioinformatics analysis |
| title | Gene Signature and Prognostic Value of Ubiquitin-Specific Proteases Members in Hepatocellular Carcinoma and Explored the Immunological Role of USP36 |
| title_full | Gene Signature and Prognostic Value of Ubiquitin-Specific Proteases Members in Hepatocellular Carcinoma and Explored the Immunological Role of USP36 |
| title_fullStr | Gene Signature and Prognostic Value of Ubiquitin-Specific Proteases Members in Hepatocellular Carcinoma and Explored the Immunological Role of USP36 |
| title_full_unstemmed | Gene Signature and Prognostic Value of Ubiquitin-Specific Proteases Members in Hepatocellular Carcinoma and Explored the Immunological Role of USP36 |
| title_short | Gene Signature and Prognostic Value of Ubiquitin-Specific Proteases Members in Hepatocellular Carcinoma and Explored the Immunological Role of USP36 |
| title_sort | gene signature and prognostic value of ubiquitin specific proteases members in hepatocellular carcinoma and explored the immunological role of usp36 |
| topic | ubiquitin-specific proteases (usps) usp36 hcc immune bioinformatics analysis |
| url | https://www.imrpress.com/journal/FBL/27/6/10.31083/j.fbl2706190 |
| work_keys_str_mv | AT weijiesun genesignatureandprognosticvalueofubiquitinspecificproteasesmembersinhepatocellularcarcinomaandexploredtheimmunologicalroleofusp36 AT jiapeishen genesignatureandprognosticvalueofubiquitinspecificproteasesmembersinhepatocellularcarcinomaandexploredtheimmunologicalroleofusp36 AT jiayingliu genesignatureandprognosticvalueofubiquitinspecificproteasesmembersinhepatocellularcarcinomaandexploredtheimmunologicalroleofusp36 AT kexinghan genesignatureandprognosticvalueofubiquitinspecificproteasesmembersinhepatocellularcarcinomaandexploredtheimmunologicalroleofusp36 AT leileiliang genesignatureandprognosticvalueofubiquitinspecificproteasesmembersinhepatocellularcarcinomaandexploredtheimmunologicalroleofusp36 AT yufenggao genesignatureandprognosticvalueofubiquitinspecificproteasesmembersinhepatocellularcarcinomaandexploredtheimmunologicalroleofusp36 |