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Endocrine Disrupting Chemicals Influence Hub Genes Associated with Aggressive Prostate Cancer
Diaaidden Alwadi1, Quentin Felty1, Changwon Yoo2
1Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA.
International Journal of Molecular Sciences
|February 25, 2023
Summary
Environmental exposures to endocrine-disrupting chemicals (EDCs) are linked to aggressive prostate cancer (PCa) through specific hub genes. This study identifies 17 EDCs affecting transcription factors that bind to key PCa genes, offering potential biomarkers for risk assessment and prognosis.
Area of Science:
- Oncology
- Environmental Health
- Bioinformatics
Background:
- Prostate cancer (PCa) is a leading cancer in men, with prevention hindered by poor understanding of environmental chemical impacts.
- Endocrine-disrupting chemicals (EDCs) may influence PCa development by mimicking hormones.
Purpose of the Study:
- Identify EDCs associated with PCa hub genes and their transcription factors (TFs).
- Analyze the protein-protein interaction (PPI) network of these genes.
- Explore the role of EDCs in PCa pathogenesis and prognosis.
Main Methods:
- Utilized six PCa microarray datasets (GSE46602, GSE38241, GSE69223, GSE32571, GSE55945, GSE26126) from NCBI/GEO.
- Performed integrated bioinformatics analysis including enrichment analysis (DAVID.6.8, GO, KEGG, STRING, MCODE, CytoHubba, GeneMANIA).
- Validated hub genes using TCGA RNA-seq data and assessed EDC influence via the Chemical-Toxicogenomic Database (CTD).
Main Results:
- Identified 369 differentially expressed genes (DEGs) linked to cancer pathways, cell division, and hormone response.
- Discovered five up-regulated (NCAPG, MKI67, TPX2, CCNA2, CCNB1) and seven down-regulated (CDK1, CCNB2, AURKA, UBE2C, BUB1B, CENPF, RRM2) hub genes.
- Found 17 EDCs affecting TFs (NFY, CETS1P54, OLF1, SRF, COMP1) that bind to PCa hub genes (NCAPG, MKI67, CCNA2, CDK1, UBE2C, CENPF).
- Hub gene expression correlated with high Gleason scores and impacted patient survival.
Conclusions:
- Validated PCa hub genes and their associated TFs offer potential molecular biomarkers.
- These biomarkers can aid in risk assessment for various EDCs implicated in aggressive PCa.
- A systems biology approach highlights the overlapping roles of EDCs in PCa prognosis.
Keywords:
endocrine disruptive chemicalsenvironmental health risk assessmentgene ontologymolecular biomarkersprostate cancerprotein–protein interactionMore Related Videos
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