Investigating the Effect of Smoking on Transcriptomics of Primary Oral Cavity Tumors using the Gene Expression Omnibus Dataset

Smoking has been suspected to have some relation with the occurrence of oral cancers. However, not much research has been documented with advanced analysis. Utilizing Gene Expression Omnibus (GSE) data, a differential expression (DE) analysis was conducted to investigate the impact of smoking on oral carcinogenesis. The dataset underwent quality control, followed by K-nearest neighbors (KNN) clustering of cells. Cell types were assigned by using the sc-type cell marker library and the annotations provided by the data contributors. Subsequently, DE analysis was performed for each identified cell type. The results of the DE analysis revealed significant upregulation of keratin-related genes, extracellular matrix (ECM) related genes, and immunoglobulin-related genes in smoker tissues. Notably, neutrophils and macrophages exhibited elevated expression of the keratin (KRT) gene family. Moreover, normal epithelial cells displayed increased expression of type 1 collagen (COL1A1). Neutrophils showed heightened expression of trefoil factor 3 (TFF3), which is associated with mucosa secretion. Furthermore, macrophages and naive CD4+ T cells exhibited elevated levels of matrix metalloproteinases (MMPs), enzymes involved in ECM degradation. Interestingly, tumor cells and fibroblasts demonstrated elevated expression of S100A7 (S100 calcium-binding protein A7), an antimicrobial peptide known to impact keratinocyte differentiation. These findings shed light on the complex molecular changes that can potentially lead to the remodeling of the local microenvironment.