A Pan-Cancer Analysis of SMARCA4 Alterations in Human Cancers

Abstract

BackgroundSMARCA4, 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.MethodsThe 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.ResultsHigh 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.ConclusionsOur study offers a comprehensive understanding of the oncogenic roles of SMARCA4 across different tumors. SMARCA4 may correlate with tumor immunity.

Delving into the Heterogeneity of Different Breast Cancer Subtypes and the Prognostic Models Utilizing scRNA-Seq and Bulk RNA-Seq

“…SOX4 increases breast cancer cell viability, migration, and invasion in vitro, and enhances tumor growth and metastasis in vivo [ 50 ]. SMARCA4 is closely related to tumor immune evasion [ 52 ]. HDAC3 is strongly expressed in a subgroup with more aggressive breast cancer [ 53 ].…”

Olfactomedin-4 improves cutaneous wound healing by promoting skin cell proliferation and migration through POU5F1/OCT4 and ESR1 signalling cascades

“…Our results are in agreement with previous findings that demonstrated a role for OLFM4 in promoting tumour cell adhesion and migration [ 9 ]. We detected activation of SMARCA4, a chromatin binding protein that is associated with tumorigenesis in a variety of tissues [ 45 ]. As SMARCA4 expression is negatively associated with CD8 + T cell infiltration of tumours [ 45 ], it has been suggested to control the magnitude and duration of inflammation.…”

“…We detected activation of SMARCA4, a chromatin binding protein that is associated with tumorigenesis in a variety of tissues [ 45 ]. As SMARCA4 expression is negatively associated with CD8 + T cell infiltration of tumours [ 45 ], it has been suggested to control the magnitude and duration of inflammation. In addition, OLFM4 stimulation was predicted to activate TLR4 signalling that is an important regulator of inflammation during cutaneous wound healing [ 46 , 47 ].…”

Clinicopathological Significance, Related Molecular Changes and Tumor Immune Response Analysis of the Abnormal SWI/SNF Complex Subunit PBRM1 in Gastric Adenocarcinoma

“…There is a significant correlation between abnormal SWI/SNF subunit and MSI-H, and both are related to PD-L1 expression, high tumor genome mutation rate, and high TIL, resulting in high tumor immune activity. There are several hypotheses regarding the causal affiliation of the two: 1) SWI/SNF complex subunit gene mutations may be caused by MSI; 2) the two may be a reflection of genome-wide hypermethylation, that is, a CpG island methylation phenotype; and 3) SWI/SNF complex deficiency leads to impaired MMR, mutation or MLH1 promoter methylation and epigenetic alterations ( 20 , 21 ). Studies have found that SWI/SNF subunit ARID1A deficiency attenuates mismatch repair (MMR) capacity, impairs mismatch repair in a variety of cancers, leads to genomic alterations in microsatellite instability ( 22 , 23 ), increases TMB, increases neoantigen presentation, increases TILs, and makes tumors susceptible to immune checkpoint blockade.…”