Woo Sangsoon, Gao Hong, Henderson David, Zacharias Wolfgang, Liu Gang, Tran Quynh T, Prasad G L
Statistical Genetics, Axio Research LLC, 4th Ave. Suite 200, Seattle, WA 98121, USA.
Department of Medicine, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Genes (Basel). 2017 May 3;8(5):132. doi: 10.3390/genes8050132.
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, and , 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 as a potential biomarker for differentiating the biological effects of combustible from non-combustible tobacco products.
吸烟已被确认为发生口腔鳞状细胞癌（OSCC）的主要危险因素，但无烟烟草制品的影响却较少受到关注。我们的目标是利用口腔细胞系确定潜在的生物标志物，以区分可燃烟草制品和不可燃烟草制品的生物学效应。将正常人牙龈上皮细胞（HGEC）、非转移性（101A）和转移性（101B）OSCC细胞系暴露于不同的烟草制品制剂（TPPs），包括香烟烟雾总颗粒物（TPM）、全烟条件培养基（WS-CM）、完全人工唾液中的无烟烟草提取物（STE）或单独的尼古丁（NIC）。我们进行了基于微阵列的基因表达谱分析，发现101A细胞系中有3456个探针集、101B细胞系中有1432个探针集以及HGEC细胞系中有2717个探针集差异表达。基因集富集分析（GSEA）显示，外源性物质代谢和类固醇生物合成是可燃TPPs上调而非不可燃TPPs上调的前两条通路。值得注意的是，醛酮还原酶基因 和 是最富集通路中的核心基因，并在统计学上被可燃TPPs上调了八倍以上。定量实时聚合酶链反应（qRT-PCR）结果在统计学上支持 将 作为区分可燃和不可燃烟草制品生物学效应的潜在生物标志物。
