Identification of Potential Hub Genes Related to Aflatoxin B1, Liver Fibrosis and Hepatocellular Carcinoma via Integrated Bioinformatics Analysis

SIMPLE SUMMARY: Aflatoxin B1 a highly distributed and hepatotoxicant leads to liver damage and the subsequent development of liver cancer. The aim is to study the combined genes and their function in liver damage progression to prevent reversible liver fibrosis which is a dynamic and bidirectional process to become irreversible liver cancer as a result of aflatoxin B1 exposure. The present study revealed that the combined differential expressed genes of AFB1-fibrosis-related and liver cancer-related were connected to cell process disruption, the top ten core genes were identified using four different algorithm methods and the combined core genes showed that the BUB1B and RRM2 genes were core genes of AFB1-liver fibrosis-liver cancer. The inflammatory-related signaling ssGSEA score for BUB1B high expression results in a significant increase in the expression of JAK-STAT regulation and TLR signaling with no effect on the RRM2 gene also the immune checkpoint chemotherapy-related high expression of the BUB1B gene was showed to have a significant change in CTLA4 Blockage in TCHA LIHC patients. Our study will contribute to, the aflatoxin b1 hepatotoxicant damaging progression could be controlled by BUB1B and RRM2 gene study. ABSTRACT: 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.