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Objective <p>This study aims to investigate the underlying molecular mechanisms linking seven prevalent air pollutants (benzene, toluene, SO<sub>2</sub>, NO<sub>2</sub>, NO, CO, and O<sub>3</sub>) to the development and occurrence of hepatocellular carcinoma (HCC).</p> Methods <p>Seven kinds of air pollutants and HCC-related genes were retrieved from several online databases, and their intersections were taken. PPI visualization analysis of intersection genes was performed. The potential biological mechanism of intersection genes was clarified by GO and KEGG enrichment analysis. Using five different algorithms to identify the core gene, the expression level of core gene in HCC was verified by TCGA database, and its diagnostic performance was evaluated by the ROC curve. Through KM survival analysis, the genes related to prognosis were further screened, and the relationship between them and immune cell infiltration was explored. The interaction between them and seven air pollutants was explored by molecular docking analysis.</p> Results <p>Seven common air pollutants and HCC-related genes have 55 cross genes. The enrichment analysis of GO and KEGG showed that these genes promoted the occurrence and development of HCC through cell carcinogenesis, signal transduction, genetic information processing, and metabolic correlation. Eight core genes were screened by five different algorithms. TCGA data confirmed that the eight core genes were differentially expressed in HCC, and ROC curve showed that all the eight core genes had a good diagnostic performance. KM survival curve further showed that six key genes were related to the poor prognosis of HCC patients. Immune infiltration analysis revealed that these six key genes play significant roles in the HCC immune microenvironment. Molecular docking further supported potential interactions between the air pollutants and these six key genes.</p> Conclusion <p>The findings indicate that ESR1, MMP9, RELA, PARP1, DNMT1, and CDK1 are critically involved in HCC pathogenesis. This research enhances public understanding of air pollution risks.</p>

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Air pollution-driven key regulators in hepatocellular carcinoma: Identification via integrated bioinformatics and network toxicology

  • 期刊论文

  • 发表日期：

    2026年4月20日

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  • Yang Wu,
  • Tian Li,
  • Jiucong Zhang,
  • Xiaofeng Zheng,
  • Xiaohui Yu

摘要

Objective

This study aims to investigate the underlying molecular mechanisms linking seven prevalent air pollutants (benzene, toluene, SO2, NO2, NO, CO, and O3) to the development and occurrence of hepatocellular carcinoma (HCC).

Methods

Seven kinds of air pollutants and HCC-related genes were retrieved from several online databases, and their intersections were taken. PPI visualization analysis of intersection genes was performed. The potential biological mechanism of intersection genes was clarified by GO and KEGG enrichment analysis. Using five different algorithms to identify the core gene, the expression level of core gene in HCC was verified by TCGA database, and its diagnostic performance was evaluated by the ROC curve. Through KM survival analysis, the genes related to prognosis were further screened, and the relationship between them and immune cell infiltration was explored. The interaction between them and seven air pollutants was explored by molecular docking analysis.

Results

Seven common air pollutants and HCC-related genes have 55 cross genes. The enrichment analysis of GO and KEGG showed that these genes promoted the occurrence and development of HCC through cell carcinogenesis, signal transduction, genetic information processing, and metabolic correlation. Eight core genes were screened by five different algorithms. TCGA data confirmed that the eight core genes were differentially expressed in HCC, and ROC curve showed that all the eight core genes had a good diagnostic performance. KM survival curve further showed that six key genes were related to the poor prognosis of HCC patients. Immune infiltration analysis revealed that these six key genes play significant roles in the HCC immune microenvironment. Molecular docking further supported potential interactions between the air pollutants and these six key genes.

Conclusion

The findings indicate that ESR1, MMP9, RELA, PARP1, DNMT1, and CDK1 are critically involved in HCC pathogenesis. This research enhances public understanding of air pollution risks.