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A Pan-Cancer Analysis of SMARCA4 Alterations in Human Cancers

SMARCA4型 癌症研究 生物 免疫检查点 ARID1A型 染色质重塑 肿瘤微环境 免疫系统 染色质 医学 免疫学 突变 免疫疗法 基因 遗传学
作者
Ling Peng,Jisheng Li,Jie Wu,Bin Xu,Zhiqiang Wang,Georgios Giamas,Justin Stebbing,Zhentao Yu
出处
期刊:Frontiers in Immunology [Frontiers Media]
卷期号:12 被引量:44
标识
DOI:10.3389/fimmu.2021.762598
摘要

SMARCA4, the essential ATPase subunit of SWI/SNF chromatin remodeling complex, regulates transcription through the control of chromatin structure and is increasingly thought to play significant roles in human cancers. This study aims to explore the potential role of SMARCA4 with a view to providing insights on pathologic mechanisms implicated here.The potential roles of SMARCA4 in different tumors were explored based on The Cancer Genome Atlas (TCGA), Genotype-tissue expression (GTEx), Tumor Immune Estimation Resource (TIMER), and Gene Set Enrichment Analysis (GSEA) datasets. The expression difference, mutation and phosphorylation status, survival, pathological stage, DNA methylation, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), tumor microenvironment (TME), and immune cell infiltration related to SMARCA4 were analyzed.High expression levels of SMARCA4 were observed in most cancer types. SMARCA4 expression in tumor samples correlates with poor overall survival in several cancers. Lung adenocarcinoma cases with altered SMARCA4 showed a poorer prognosis. Enhanced phosphorylation levels of S613, S695, S699, and S1417 were observed in several tumors, including breast cancer. SMARCA4 correlated with tumor immunity and associated with different immune cells and genes in different cancer types. TMB, MSI, MMR, and DNA methylation correlated with SMARCA4 dysregulation in cancers. SMARCA4 expression was negatively associated with CD8+ T-cell infiltration in several tumors. Furthermore, the SWI/SNF superfamily-type complex and ATPase complex may be involved in the functional mechanisms of SMARCA4, albeit these data require further confirmation.Our study offers a comprehensive understanding of the oncogenic roles of SMARCA4 across different tumors. SMARCA4 may correlate with tumor immunity.
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