Khaleel Anas, Alkhawaja Bayan, Al-Qaisi Talal Salem, Alshalabi Lubna, Tarkhan Amneh H
Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan.
Department of Pharmaceutical Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan.
Egypt J Med Hum Genet. 2022;23(1):69. doi: 10.1186/s43042-022-00268-y. Epub 2022 Mar 17.
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.
The gene expression dataset (accession number GSE8987, GPL96) of buccal mucosa samples from smokers ( = 5) and never smokers ( = 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.
A total of 459 genes were found to be significantly differentially expressed in smoker buccal mucosa ( < 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.
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.
The online version contains supplementary material available at 10.1186/s43042-022-00268-y.
吸烟是全球可预防的主要死亡原因，也是口腔癌最常见的病因。本研究旨在更深入地了解口腔中因接触香烟烟雾而改变的分子途径。
从美国国立生物技术信息中心（NCBI）的基因表达综合数据库（GEO）中下载吸烟者（n = 5）和从不吸烟者（n = 5）颊黏膜样本的基因表达数据集（登录号GSE8987，GPL96）。通过NCBI的GEO2R软件确定差异表达，并使用 Ingenuity Pathway Analysis（IPA）软件进行通路分析。
共发现459个基因在吸烟者颊黏膜中显著差异表达（P < 0.05）。其中261个基因过度表达，198个基因表达不足。IPA预测的主要经典通路是巨噬细胞中的一氧化氮和活性氧产生、类风湿性关节炎中的巨噬细胞/成纤维细胞和内皮细胞以及甲状腺癌通路。IPA上游分析预测TP53、APP、SMAD3和TNF蛋白以及地塞米松药物将是主要的转录调节因子。
IPA突出了致癌的关键途径，主要是巨噬细胞中的一氧化氮和活性氧产生，并证实了因接触香烟烟雾导致颊黏膜广泛损伤。我们的研究结果表明，吸烟对颊黏膜中的基因通路有显著影响，并可能突出治疗吸烟影响的潜在靶点。
在线版本包含可在10.1186/s43042-022-00268-y获取的补充材料。
