AURKA, BIRC5 and AURKB as core signature genes associated with endocrine-disrupting chemical exposure in Hepatocellular carcinoma

PURPOSE: This study aimed to systematically explore the molecular mechanisms of Hepatocellular carcinoma (HCC) induced by endocrine-disrupting chemicals (EDCs) and identify core signature genes with clinical utility. METHODS: Bioinformatics analysis, machine learning, and in vitro experiments were integrated. TCGA-LIHC (The Cancer Genome Atlas-Liver Hepatocellular carcinoma) and GSE76427 datasets were used for target screening and validation. Toxicological analysis, target prediction, functional enrichment, Protein-protein interaction (PPI) network, and three machine learning algorithms were applied to prioritize signature genes. In vitro experiments verified the effects of single EDC on HCC cells and gene dependence. RESULTS: AURKA (Aurora Kinase A), BIRC5 (Baculoviral IAP Repeat Containing 5) and AURKB (Aurora Kinase B) were identified as core signature genes, consistently upregulated in HCC with AUC (area under the curve) > 0.77. Their low expression correlated with better survival rate. EDCs (e.g., MBP) promoted HCC proliferation and invasion, which was dependent on AURKA. Signature genes negatively correlated with anti-tumor immune infiltration. CONCLUSION: AURKA, BIRC5, and AURKB were identified as candidate biomarkers and therapeutic targets potentially mediating EDC-induced HCC, providing insights into EDC-related hepatocarcinogenesis mechanisms.