Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme.
Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme.
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DOI：
10.3389/fimmu.2022.842524
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发表时间：
2022
影响因子：
7.3
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中科院分区：
文献类型：
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Ankyrin repeat and SOCS Box containing 3（ASB 3）是一种E3泛素连接酶。有报道称其调节某些癌症的进展，但尚未进行系统的泛癌分析以探讨其在预后和免疫微环境中的功能。在这项研究中，mRNA表达数据从TCGA和GTEx数据库下载。将来自通过神经外科手术切除的14个多形性胶质母细胞瘤（GBM）样品的下一代测序数据用作验证数据集。应用ssGSEA、Kaplan-Meier、考克斯回归分析、GSEA和在线工具等多种生物信息学方法，研究GBM中ASB 3的表达、基因活性、患者预后及其与临床信息、免疫微环境和相关信号通路的相关性。使用动物模型验证了ASB 3在肿瘤浸润淋巴细胞（TIL）中的生物学功能。我们发现ASB 3在多种肿瘤中异常表达，特别是在GBM中，并且与癌症患者的预后显著相关。在某些肿瘤中，ASB 3水平与TMB、MSI及免疫细胞浸润有关。ASB 3与免疫浸润和TME呈负相关，包括GBM中的调节性T细胞（TME）、癌相关成纤维细胞、免疫抑制因子和相关信号通路。ASB 3过表达可降低TIL中Tcl 3的比例。GSEA和PPI分析也显示GBM中ASB 3表达与致癌信号通路呈负相关。ASB 3的全面泛癌症分析显示其作为癌症预后的生物标志物和有效预测免疫治疗反应的潜在功能。本研究不仅丰富了对ASB 3在泛肿瘤尤其是GBM免疫中生物学功能的认识，也为GBM的个体化免疫治疗提供了新的参考。
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. 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. 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. 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.