Genomic and transcriptomic insights into aflatoxin-induced intrahepatic cholangiocarcinoma: an integrated pathway and meta-analysis study

作者：Fengping Li, Yuanyang Ma, Yan Cheng, Shanshan Zou · 发表于：Frontiers in Genetics · 年份：2026 · DOI：10.3389/fgene.2026.1785259 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Mycotoxins in Agriculture and Food、Ferroptosis and cancer prognosis

Introduction: Environmental and chemical exposures are major yet incompletely characterized drivers of human carcinogenesis. Aflatoxin, a potent food-borne mycotoxin, has been implicated in tumor initiation, proliferation, and immune suppression in intrahepatic cholangiocarcinoma (ICC), but its genomic mechanisms remain poorly defined. Methods: We employed extensive literature data mining (LDM) to identify genes associated with both aflatoxin exposure and ICC, enabling construction of a mechanistic genetic pathway linking exposure to disease. These pathways were further evaluated using a meta-analysis of five Gene Expression Omnibus (GEO) expression datasets, followed by functional annotation to characterize their biological roles. Results: LDM identified 1,754 ICC-associated genes, of which 427 were also linked to aflatoxin, with 154 positioned as potential intermediate regulators connecting aflatoxin exposure to ICC. Meta-analysis revealed significant expression alterations in six genes upon aflatoxin exposure, including upregulation of CRP, CDK2, AXL, and MIR221 (overexpression >50%, p < 0.05) and downregulation of F2 and BUB1B (reduced expression >60%, p < 0.014). Co-expression analysis indicated strong interactions among these regulators (Fisher's Z > 0.53, p < 0.05), suggesting coordinated molecular responses associated with ICC progression. Functional annotation further highlighted inflammatory responses, cytokine dysregulation, and kinase-related signaling as key proc...