Baldi Salem, He Yun, Ivanov Igor, Khamgan Hassan, Safi Mohammed, Alradhi Mohammed, Shopit Abdullah, Al-Danakh Abdullah, Al-Nusaif Murad, Gao Yaping, Tian Hui
Research Center of Molecular Diagnostics and Sequencing, Axbio Biotechnology (Shenzhen) Co.,Ltd, Shenzhen, Guangdong, China.
Department of Molecular Diagnostics and Therapeutics, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat, Egypt.
Front Genet. 2022 Oct 14;13:914354. doi: 10.3389/fgene.2022.914354. eCollection 2022.
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. 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. 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.
了解肿瘤微环境（TME）和免疫细胞浸润（ICI）可能有助于指导结肠癌（COAD）的免疫治疗。然而，ARID1B是否真的受高甲基化调控或与免疫浸润有关仍不清楚。目前的工作聚焦于COAD中ARID1B基因的表达和甲基化，以及它与ICI的关系。基于TCGA的多种工具被用于分析ARID1B基因表达、DNA甲基化的差异，及其与COAD患者各种临床病理特征、体细胞突变、拷贝数变异和预后的关联。根据分析结果，mRNA高、甲基化水平低的患者总体生存率优于mRNA低、甲基化水平高的患者。免疫细胞浸润与免疫检查点基因表达的相关性分析表明，COAD中主要ICI亚型、癌症相关成纤维细胞和髓样细胞的浸润率显著富集且与ARID1B相关。通过将ICI指标与COAD微环境免疫细胞组成中的ARID1B表达相关联，发现了ARID1B表达与COAD免疫浸润之间的关联。值得注意的是，M2趋化因子与ARID1B表达相关，而M1趋化因子则不然。本研究提供了证据表明ARID1B可能在COAD的发病机制中起作用。未来需要研究导致COAD中ARID1B下调的具体潜在机制。
