Abstract
Smoking has been established as a major risk factor for developing oral squamous cell carcinoma (OSCC), but less attention has been paid to the effects of smokeless tobacco products. Our objective is to identify potential biomarkers to distinguish the biological effects of combustible tobacco products from those of non-combustible ones using oral cell lines. Normal human gingival epithelial cells (HGEC), non-metastatic (101A) and metastatic (101B) OSCC cell lines were exposed to different tobacco product preparations (TPPs) including cigarette smoke total particulate matter (TPM), whole-smoke conditioned media (WS-CM), smokeless tobacco extract in complete artificial saliva (STE), or nicotine (NIC) alone. We performed microarray-based gene expression profiling and found 3456 probe sets from 101A, 1432 probe sets from 101B, and 2717 probe sets from HGEC to be differentially expressed. Gene Set Enrichment Analysis (GSEA) revealed xenobiotic metabolism and steroid biosynthesis were the top two pathways that were upregulated by combustible but not by non-combustible TPPs. Notably, aldo-keto reductase genes, AKR1C1 and AKR1C2, were the core genes in the top enriched pathways and were statistically upregulated more than eight-fold by combustible TPPs. Quantitative real time polymerase chain reaction (qRT-PCR) results statistically support AKR1C1 as a potential biomarker for differentiating the biological effects of combustible from non-combustible tobacco products.
Highlights
Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck, with a worldwide incidence of 300,000 new cases annually
The analysis suggested that AKR1C1 and AKR1C2, members of the aldo-keto reductase family, were the two core genes induced by combustible but not by smokeless tobacco product preparations (TPPs)
In human gingival epithelial cells (HGEC), the gene expression profiles affected by total particulate matter (TPM) and whole-smoke conditioned media (WS-CM) clustered together and separated from the cluster of non-combustible TPPs, in which low-NIC and high-NIC grouped with low-smokeless tobacco extract (STE)
Summary
Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck, with a worldwide incidence of 300,000 new cases annually. One of the major risk factors for OSCC is exposure to cigarette smoke, considered to be responsible for 50–90% of cases worldwide, and the incidence of OSCC in cigarette smokers is 7–10 times higher than never smokers [1,2,3]. Cigarette smoking is a major risk factor for lung cancer, chronic obstructive pulmonary disease, and coronary heart disease, compared to non-tobacco users. Genes 2017, 8, 132 that relative to cigarette smoking, use of smokeless tobacco is significantly less harmful for lung cancer, chronic obstructive pulmonary disease, and oral cancer [4,5]. Compared to non-tobacco users, users of smokeless tobacco experience a modest increase for coronary heart disease, that risk is significantly less compared to smokers [6]. A continuum of risk exits among tobacco products [7]
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