Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme
BackgroundAnkyrin repeat and SOCS Box containing 3 (ASB3) is an E3 ubiquitin ligase. It has been reported to regulate the progression of some cancers, but no systematic pan-cancer analysis has been conducted to explore its function in prognosis and immune microenvironment.MethodIn this study, mRNA e...
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| Format: | Article |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.842524/full |
| _version_ | 1798003966746820608 |
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| author | Long Mu Zhibin Han Shengkun Yu Aowen Wang Dongjiang Chen Sijia Kong Yifei Gu Lin Xu Axiang Liu Ruohan Sun Yu Long |
| author_facet | Long Mu Zhibin Han Shengkun Yu Aowen Wang Dongjiang Chen Sijia Kong Yifei Gu Lin Xu Axiang Liu Ruohan Sun Yu Long |
| author_sort | Long Mu |
| collection | DOAJ |
| description | BackgroundAnkyrin repeat and SOCS Box containing 3 (ASB3) is an E3 ubiquitin ligase. It has been reported to regulate the progression of some cancers, but no systematic pan-cancer analysis has been conducted to explore its function in prognosis and immune microenvironment.MethodIn this study, mRNA expression data were downloaded from TCGA and GTEx database. Next generation sequencing data from 14 glioblastoma multiforme (GBM) samples by neurosurgical resection were used as validation dataset. Multiple bioinformatics methods (ssGSEA, Kaplan-Meier, Cox regression analysis, GSEA and online tools) were applied to explore ASB3 expression, gene activity, prognosis of patients in various cancers, and its correlation with clinical information, immune microenvironment and pertinent signal pathways in GBM. The biological function of ASB3 in tumor-infiltrating lymphocytes (TILs) was verified using an animal model.ResultsWe found that ASB3 was aberrant expressed in a variety of tumors, especially in GBM, and significantly correlated with the prognosis of cancer patients. The level of ASB3 was related to the TMB, MSI and immune cell infiltration in some cancer types. ASB3 had a negative association with immune infiltration and TME, including regulatory T cells (Tregs), cancer-associated fibroblasts, immunosuppressors and related signaling pathways in GBM. ASB3 overexpression reduced the proportion of Tregs in TILs. GSEA and PPI analysis also showed negative correlation between ASB3 expression and oncogenetic signaling pathways in GBM.ConclusionA comprehensive pan-cancer analysis of ASB3 showed its potential function as a biomarker of cancer prognosis and effective prediction of immunotherapy response. This study not only enriches the understanding of the biological function of ASB3 in pan-cancer, especially in GBM immunity, but also provides a new reference for the personalized immunotherapy of GBM. |
| first_indexed | 2024-04-11T12:16:00Z |
| format | Article |
| id | doaj.art-5206beb763b346aeb3e194495040353d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T12:16:00Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-5206beb763b346aeb3e194495040353d2022-12-22T04:24:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.842524842524Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiformeLong Mu0Zhibin Han1Shengkun Yu2Aowen Wang3Dongjiang Chen4Sijia Kong5Yifei Gu6Lin Xu7Axiang Liu8Ruohan Sun9Yu Long10Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDivision of Neuro-Oncology and Preston A. Wells, Jr. Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, United StatesObstetrics and Gynecology Department, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaBackgroundAnkyrin repeat and SOCS Box containing 3 (ASB3) is an E3 ubiquitin ligase. It has been reported to regulate the progression of some cancers, but no systematic pan-cancer analysis has been conducted to explore its function in prognosis and immune microenvironment.MethodIn this study, mRNA expression data were downloaded from TCGA and GTEx database. Next generation sequencing data from 14 glioblastoma multiforme (GBM) samples by neurosurgical resection were used as validation dataset. Multiple bioinformatics methods (ssGSEA, Kaplan-Meier, Cox regression analysis, GSEA and online tools) were applied to explore ASB3 expression, gene activity, prognosis of patients in various cancers, and its correlation with clinical information, immune microenvironment and pertinent signal pathways in GBM. The biological function of ASB3 in tumor-infiltrating lymphocytes (TILs) was verified using an animal model.ResultsWe found that ASB3 was aberrant expressed in a variety of tumors, especially in GBM, and significantly correlated with the prognosis of cancer patients. The level of ASB3 was related to the TMB, MSI and immune cell infiltration in some cancer types. ASB3 had a negative association with immune infiltration and TME, including regulatory T cells (Tregs), cancer-associated fibroblasts, immunosuppressors and related signaling pathways in GBM. ASB3 overexpression reduced the proportion of Tregs in TILs. GSEA and PPI analysis also showed negative correlation between ASB3 expression and oncogenetic signaling pathways in GBM.ConclusionA comprehensive pan-cancer analysis of ASB3 showed its potential function as a biomarker of cancer prognosis and effective prediction of immunotherapy response. This study not only enriches the understanding of the biological function of ASB3 in pan-cancer, especially in GBM immunity, but also provides a new reference for the personalized immunotherapy of GBM.https://www.frontiersin.org/articles/10.3389/fimmu.2022.842524/fullglioblastoma multiformeE3 ubiquitin ligasesASB3tumor microenvironmentTregs |
| spellingShingle | Long Mu Zhibin Han Shengkun Yu Aowen Wang Dongjiang Chen Sijia Kong Yifei Gu Lin Xu Axiang Liu Ruohan Sun Yu Long Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme Frontiers in Immunology glioblastoma multiforme E3 ubiquitin ligases ASB3 tumor microenvironment Tregs |
| title | Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme |
| title_full | Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme |
| title_fullStr | Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme |
| title_full_unstemmed | Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme |
| title_short | Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme |
| title_sort | pan cancer analysis of asb3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme |
| topic | glioblastoma multiforme E3 ubiquitin ligases ASB3 tumor microenvironment Tregs |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.842524/full |
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