Meta-analysis Identifies Key Genes and Pathways Implicated in Benzo[a]pyrene Exposure Response

Details

• Alternative Title:
  Chemosphere
• Personal Author:
  Zhu, Mingze ; Hwang, Jooyeon ; Xu, Chao
• Description:
  Introduction:
  
  Benzo[a]pyrene (B[a]P) is a carcinogenic polycyclic aromatic hydrocarbon that poses significant risks to human health. B[a]P influences cellular processes via intricate interactions; however, a comprehensive understanding of B[a]P’s effects on the transcriptome remains elusive. This study aimed to conduct a comprehensive analysis focused on identifying relevant genes and signaling pathways affected by B[a]P exposure and their impact on human gene expression.
  
  Methods:
  
  We searched the Gene Expression Omnibus database and identified four studies involving B[a]P exposure in human cells (T lymphocytes, hepatocellular carcinoma cells, and C3A cells). We utilized two approaches for differential expression analysis: the LIMMA package and linear regression. A meta-analysis was utilized to combine log fold changes (FC) and p-values from the identified studies using a random effects model. We identified significant genes at a Bonferroni-adjusted significance level of 0.05 and determined overlapping genes across datasets. Pathway enrichment analysis elucidated key cellular processes modulated by B[a]P exposure.
  
  Results:
  
  The meta-analysis revealed significant upregulation of CYP1B1 (log FC = 1.15, 95% CI: 0.51-1.79, P < 0.05, I2 = 82%) and ASB2 (log FC = 0.44, 95% CI: 0.20-0.67, P < 0.05, I2 = 40%) in response to B[a]P exposure. Pathway analyses identified 26 significantly regulated pathways, with the top including Aryl Hydrocarbon Receptor Signaling (P = 0.00214) and Xenobiotic Metabolism Signaling (P = 0.00550). Key genes CYP1A1, CYP1B1, and CDKN1A were implicated in multiple pathways, highlighting their roles in xenobiotic metabolism, oxidative stress response, and cell cycle regulation.
  
  Conclusion:
  
  The results provided insights into the mechanisms of B[a]P toxicity, highlighting CYP1B1’s key role in B[a]P bioactivation. The findings underscored the complexity of B[a]P’s mechanisms of action and their potential implications for human health. The identified genes and pathways provided a foundation for further exploration and enhanced our understanding of the multifaceted biological activities associated with B[a]P exposure.
  
  
• Subjects:
  Benzo(a)pyrene Cytochrome P-450 CYP1B1 Humans Receptors, Aryl Hydrocarbon Signal Transduction Transcriptome
• Keywords:
  ASB2 Benzo[a]pyrene CYP1B1 Gene Expression Meta-analysis
• Source:
  Chemosphere. 364:143121
• Pubmed ID:
  39154768
• Pubmed Central ID:
  PMC11424241
• Document Type:
  Journal Article
• Funding:
  K01 OH011891/OH/NIOSH CDC HHSUnited States/ ; T42 OH008421/OH/NIOSH CDC HHSUnited States/ ; U19 AG055373/AG/NIA NIH HHSUnited States/
• Volume:
  364
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:2b09ef5ef9f33c678cc0f3671d3c693c3c6c39b85f8edd7776a932dfa40e2ae13fbca083b6dc4ac25ff336dab1766b11eab56fa7f3cbd0564924fa933e492142
• Download URL:
  https://stacks.cdc.gov/view/cdc/164024/cdc_164024_DS1.pdf
• File Type:
  [PDF - 838.91 KB ]