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Updated: Jul 20, 2025
Impact Assessment of Repeated Exposure of Organotypic 3D Bronchial and Nasal Tissue Culture Models to Whole Cigarette Smoke
Published on: February 12, 2015
Pathway analysis of smoking-induced changes in buccal mucosal gene expression
Anas Khaleel1, Bayan Alkhawaja2, Talal Salem Al-Qaisi3
1Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan.
Background:
Cigarette smoking is the leading preventable cause of death worldwide, and it is the most common cause of oral cancers. This study aims to provide a deeper understanding of the molecular pathways in the oral cavity that are altered by exposure to cigarette smoke.
Methods:
The gene expression dataset (accession number GSE8987, GPL96) of buccal mucosa samples from smokers (n = 5) and never smokers (n = 5) was downloaded from The National Center for Biotechnology Information's (NCBI) Gene Expression Omnibus (GEO) repository. Differential expression was ascertained via NCBI's GEO2R software, and Ingenuity Pathway Analysis (IPA) software was used to perform a pathway analysis.
Results:
A total of 459 genes were found to be significantly differentially expressed in smoker buccal mucosa (p < 0.05). A total of 261 genes were over-expressed while 198 genes were under-expressed. The top canonical pathways predicted by IPA were nitric oxide and reactive oxygen production at macrophages, macrophages/fibroblasts and endothelial cells in rheumatoid arthritis, and thyroid cancer pathways. The IPA upstream analysis predicted that the TP53, APP, SMAD3, and TNF proteins as well as dexamethasone drug would be top transcriptional regulators.
Conclusions:
IPA highlighted critical pathways of carcinogenesis, mainly nitric oxide and reactive oxygen production at macrophages, and confirmed widespread injury in the buccal mucosa due to exposure to cigarette smoke. Our findings suggest that cigarette smoking significantly impacts gene pathways in the buccal mucosa and may highlight potential targets for treating the effects of cigarette smoking.
Supplementary Information:
The online version contains supplementary material available at 10.1186/s43042-022-00268-y.
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