AI Article Synopsis
- Hepatocellular carcinoma (HCC) is a common cancer, and understanding mutations in the ARID1A gene may help identify new treatments for patients.
- Researchers used cBioPortal to analyze ARID1A genetic changes in HCC cases and found a mutation occurrence of 9.35%, which was linked to poorer patient survival rates.
- Experimental results confirmed that ARID1A functions as a tumor suppressor, with low expression correlating to worse outcomes, indicating that ARID1A could serve as a valuable biomarker and treatment target for HCC.
Article Abstract
Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Clarification of the somatic mutational landscape of important genes could reveal new therapeutic targets and facilitate individualized therapeutic approaches for HCC patients. The mutation and expression changes in the ARID1A gene in HCC remain controversial.
Methods: First, cBioPortal was used to visualize genetic alterations and DNA copy number alterations (CNAs) in ARID1A. The relationships between ARID1A mutation status and HCC patient clinicopathological features and overall survival (OS) were also determined. Then, a meta-analysis was performed to evaluate the effect of ARID1A mutation or expression on the prognosis of HCC patients. Finally, the role of ARID1A in HCC progression was verified by experiments.
Results: ARID1A mutation was detected in 9.35% (33/353) of sequenced HCC cases, and ARID1A mutation decreased ARID1A mRNA expression. Patients with ARID1A alterations presented worse OS than those without ARID1A alterations. Meta-analysis and human HCC tissue microarray (TMA) analysis revealed that HCC patients with low ARID1A expression had worse OS and relapse-free survival (RFS), and low ARID1A expression was negatively correlated with tumour size. Then, ARID1A gain-of-function and loss-of-function experiments demonstrated the tumour suppressor role of ARID1A in HCC . In terms of the mechanism, we found that ARID1A could inhibit HCC progression by regulating retinoblastoma-like 1 (RBL1) expression via the JNK/FOXO3 pathway.
Conclusions: ARID1A can be considered a potential prognostic biomarker and candidate therapeutic target for HCC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10025035 | PMC |
| http://dx.doi.org/10.1016/j.heliyon.2023.e14307 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Adenoid cystic carcinomas (AdCC) of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost universal presence of the gene fusion MYB::NFIB, or less commonly MYBL1::NFIB. Sinonasal AdCC is an aggressive salivary gland malignancy with no effective systemic therapy. Therefore, it is urgent to search for potentially targetable genetic alterations associated with AdCC.
View Article and Find Full Text PDFImpaired ARID1A expression attenuated the immune response in gastric cancer via histone acetylation.
Clin Epigenetics
January 2025
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Background: The primary objective of this study was to examine whether ARID1A mutations confer a fitness advantage to gastric cancer from an immunological perspective, along with elucidating the underlying mechanism. Additionally, we aimed to identify the clinical potential of combining epigenetic inhibitors with immune checkpoint inhibitors to improve the efficacy of immunotherapy for gastric cancer.
Methods: The correlation between ARID1A gene expression and gastric cancer patient survival was analyzed using the GEO dataset GSE62254.
Efficacy of glutathione inhibitor eprenetapopt against the vulnerability of glutathione metabolism in SMARCA4-, SMARCB1- and PBRM1-deficient cancer cells.
Sci Rep
December 2024
Division of Cancer Therapeutics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Mutation of genes related to the SWI/SNF chromatin remodeling complex is detected in 20% of all cancers. The SWI/SNF chromatin remodeling complex comprises about 15 subunits and is classified into three subcomplexes: cBAF, PBAF, and ncBAF. Previously, we showed that ovarian clear cell carcinoma cells deficient in ARID1A, a subunit of the cBAF complex, are synthetic lethal with several genes required for glutathione (GSH) synthesis and are therefore sensitive to the GSH inhibitor eprenetapopt (APR-246).
View Article and Find Full Text PDFLoss of SMARCA4 induces sarcomatogenesis through epithelial-mesenchymal transition in ovarian carcinosarcoma.
Cancer Sci
December 2024
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ovarian carcinosarcoma (OCS) is a rare and aggressive tumor, and the development of its sarcomatous component is believed to be due to epithelial-mesenchymal transition (EMT). The SWIch/sucrose nonfermentable chromatin remodeling factor (CRF) is closely related to EMT; however, the relationship between CRF and EMT in OCS remains unclear. In this study, we analyzed the protein expression of CRFs, including ARID1A and SMARCA4, and their downstream mRNA expression in 28 OCS cases, two fallopian tube CS cases, and one peritoneal CS case.
View Article and Find Full Text PDFPolysplenia and developmental delay in a case of microduplication in the 1p36.11 region involving the ARID1A gene.
Congenit Anom (Kyoto)
January 2025
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!