Aberrantly hypermethylated ARID1B is a novel biomarker and potential therapeutic target of colon adenocarcinoma

• Published in: Frontiers in genetics Vol. 13; p. 914354
• Main Authors: Baldi, Salem, He, Yun, Ivanov, Igor, Khamgan, Hassan, Safi, Mohammed, Alradhi, Mohammed, Shopit, Abdullah, Al-Danakh, Abdullah, Al-Nusaif, Murad, Gao, Yaping, Tian, Hui
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 14.10.2022
• Subjects: ARID1B; Colon adenocarcinoma; DNA Methylation; Genetics; Immune Cell Infiltration; RNA expression; TCGA
• ISSN: 1664-8021; 1664-8021
• DOI: 10.3389/fgene.2022.914354

Background and Objective: Understanding the tumor microenvironment (TME) and immune cell infiltration (ICI) may help guide immunotherapy efforts for colon cancer (COAD). However, whether ARID1B is truly regulated by hypermethylation or linked to immune infiltration remains unknown. The current work focused on the ARID1B gene expression and methylation in COAD, as well as its relation with ICI. Methods and Results: Multiple tools based on TCGA were used to analyze the differences in the expression of the ARID1B gene, DNA methylation, and its association with various clinicopathological features, somatic mutations, copy number variation, and the prognosis of patients with COAD. According to the analysis results, patients with high mRNA, low methylation levels showed better overall survival than patients with low mRNA, high methylation levels. The correlation analysis of immune cell infiltration and immune checkpoint gene expression showed that the infiltration rates of the main ICI subtypes, cancer-associated fibroblast, and myeloid cells were significantly enriched and correlated with ARID1B in COAD. An association between ARID1B expression and immune infiltration in COAD was found by correlating ICI indicators with ARID1B expression in the immune cell composition of the COAD microenvironment. Notably, M2 chemokines were related to ARID1B expression, while M1 chemokines were not. Conclusion: This study provided evidence that ARID1B may have a role in the pathogenesis of COAD. The specific underlying mechanisms that could be responsible for ARID1B’s downregulation in COAD will need to be investigated in the future.