Fu Yingzhou, Xie Wei, Ren Qifan, Wu Jiao, Long Ying, Liu Ying
Hunan Provincial Clinical Research Centre for Oncoplastic Surgery, Hunan Cancer Hospital / The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, PR China.
The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, PR China.
Sci Rep. 2025 Jul 22;15(1):26542. doi: 10.1038/s41598-025-10669-9.
Colon cancer is a highly aggressive solid tumor. Because most studies have focused on the intrinsic oncogenic pathways of tumors, we focused on the relationship between DNA methylation genes in the tumor immune microenvironment and colon cancer prognosis. We download RNA-seq data from the TCGA dataset. DNA methylation genes were scored using the GSVA method, and this score was subjected to GSEA, GO and KEGG enrichment analysis. Then, in vitro experiments examined the effect of silencing LARS2 on the proliferation and apoptosis of HCT116 cells. We obtained 2635 genes, 144 were obtained after single factor screening, and 8 genes were obtained through random forest dimensionality reduction. They are LARS2, TEX2, BRIP1, QSOX2, HOOK1, COX19, NEK4 and STXBP4. Survival analysis indicated that patients with high Riskscore had poor prognosis. There were significant differences in the expression of DNA methylation genes between the two groups with high and low Riskscore. The immune checkpoints of different Riskscore groups include Antigen present, Ligand, Receptor, Co-inhibitor, Co-stimulator, Other, and Cell adhesion. There were significant differences in the expression of genes and DNA integrity checkpoint, histone deacetylation, mitotic DNA damage checkpoint, TGF-beta signaling pathway, Platinum drug resistance and Protein processing in endoplasmic reticlum pathway at the level of Antigen present. Silencing of LARS2 decreased the proliferative capacity and increased the apoptosis rate of HCT116. Our findings suggest that LARS2 methylation could affects colon cancer development.
结肠癌是一种侵袭性很强的实体瘤。由于大多数研究都集中在肿瘤的内在致癌途径上,我们聚焦于肿瘤免疫微环境中DNA甲基化基因与结肠癌预后之间的关系。我们从TCGA数据集中下载了RNA测序数据。使用GSVA方法对DNA甲基化基因进行评分,并对该评分进行基因集富集分析(GSEA)、基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。然后,体外实验检测了沉默亮氨酰-tRNA合成酶2(LARS2)对人结肠癌细胞系HCT116增殖和凋亡的影响。我们获得了2635个基因,单因素筛选后得到144个,通过随机森林降维得到8个。它们是LARS2、TEX2、BRIP1、QSOX2、HOOK1、COX19、NEK4和STXBP4。生存分析表明,高风险评分的患者预后较差。高风险评分组和低风险评分组之间DNA甲基化基因的表达存在显著差异。不同风险评分组的免疫检查点包括抗原呈递、配体、受体、共抑制分子、共刺激分子以及其他分子和细胞黏附分子。在抗原呈递水平上,不同风险评分组在基因表达和DNA完整性检查点、组蛋白去乙酰化、有丝分裂DNA损伤检查点、转化生长因子-β信号通路、铂类药物耐药性以及内质网中的蛋白质加工途径方面存在显著差异。沉默LARS2可降低HCT116的增殖能力并增加其凋亡率。我们的研究结果表明,LARS2甲基化可能影响结肠癌的发展。