Hamdy Hayam, Yang Yi, Cheng Cheng, Liu Qizhan
Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, New Valley University, New Valley 72713, Egypt.
Biology (Basel). 2023 Jan 29;12(2):205. doi: 10.3390/biology12020205.
The molecular mechanism of the hepatotoxicant aflatoxin B1 to induce liver fibrosis and hepatocellular carcinoma (HCC) remains unclear, to offer fresh perspectives on the molecular mechanisms underlying the onset and progression of AFB1-Fibrosis-HCC, which may offer novel targets for the detection and therapy of HCC caused by AFB1. In this study, expression profiles of AFB1, liver fibrosis and liver cancer-related datasets were downloaded from the Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) were identified by the GEO2R tool. The STRING database, CytoHubba, and Cytoscape software were used to create the protein-protein interaction and hub genes of the combined genes, and the ssGSEA score for inflammatory cells related gene sets, the signaling pathway, and immunotherapy were identified using R software and the GSEA database. The findings revealed that AFB1-associated liver fibrosis and HCC combined genes were linked to cell process disruptions, the BUB1B and RRM2 genes were identified as hub genes, and the BUB1B gene was significantly increased in JAK-STAT signaling gene sets pathways as well as having an immunotherapy-related impact. In conclusion, BUB1B and RRM2 were identified as potential biomarkers for AFB1-induced fibrosis and HCC progression.
肝毒性物质黄曲霉毒素B1诱导肝纤维化和肝细胞癌（HCC）的分子机制仍不清楚，旨在为AFB1-纤维化-HCC发病和进展的分子机制提供新的视角，这可能为AFB1所致HCC的检测和治疗提供新的靶点。在本研究中，从基因表达综合数据库（GEO）下载了AFB1、肝纤维化和肝癌相关数据集的表达谱，并通过GEO2R工具鉴定了差异表达基因（DEG）。利用STRING数据库、CytoHubba和Cytoscape软件构建了组合基因的蛋白质-蛋白质相互作用和枢纽基因，并使用R软件和GSEA数据库鉴定了炎症细胞相关基因集、信号通路和免疫治疗的单样本基因集富集分析（ssGSEA）分数。研究结果显示，AFB1相关的肝纤维化和HCC组合基因与细胞过程破坏有关，BUB1B和RRM2基因被鉴定为枢纽基因，BUB1B基因在JAK-STAT信号基因集通路中显著增加，并且具有与免疫治疗相关的影响。总之，BUB1B和RRM2被鉴定为AFB1诱导的纤维化和HCC进展的潜在生物标志物。
