Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme

Long Mu; Zhibin Han; Shengkun Yu; Aowen Wang; Dongjiang Chen; Sijia Kong; Yifei Gu; Lin Xu; Axiang Liu; Ruohan Sun; Yu Long

doi:10.3389/fimmu.2022.842524

Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme

Front Immunol. 2022 Dec 21:13:842524. doi: 10.3389/fimmu.2022.842524. eCollection 2022.

Authors

Long Mu¹, Zhibin Han¹, Shengkun Yu¹, Aowen Wang¹, Dongjiang Chen², Sijia Kong³, Yifei Gu¹, Lin Xu¹, Axiang Liu¹, Ruohan Sun⁴, Yu Long¹

Affiliations

¹ Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
² Division 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 States.
³ Obstetrics and Gynecology Department, Peking University Shenzhen Hospital, Shenzhen, China.
⁴ Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Abstract

Background: Ankyrin 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.

Method: In 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.

Results: We 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.

Conclusion: A 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.

Keywords: ASB3; E3 ubiquitin ligases; Tregs; glioblastoma multiforme; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cancer-Associated Fibroblasts*
Carcinogenesis
Cell Transformation, Neoplastic
Computational Biology
Glioblastoma* / genetics
Tumor Microenvironment / genetics