Abstract
Objective Oral leukoplakia (OLK) is the most common precancerous lesion in the oral cavity. This study aimed to explore key biomarkers for monitoring OLK for early diagnosis of oral squamous cell carcinoma (OSCC) and screen small-molecule drugs for the prevention of OSCC. Method The Gene Expression Omnibus (GEO) database was explored to extract two microarray datasets, namely, GSE85195 and GSE25099. The data of the normal group, OLK group, and OSCC group were analyzed by weighted gene coexpression network analysis (WGCNA) to identify the most significant gene module and differentially expressed genes (DEGs). The intersection genes were extracted as the key genes of OLK carcinogenesis. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed in the module. Connectivity Map and molecular docking were used to screen small-molecule drugs. The diagnostic values of four key genes were identified and verified in the GSE26549 dataset. Results WGCNA obtained the red module (r = −0.91, p < 0.05) with the strongest correlation with cancerous phenotype. GO enrichment analysis showed 60 pathways, including 28 biological processes, 11 cell components, and 21 molecular functions, and KEGG enrichment analysis showed 4 pathways (p < 0.05). In the differential expression analysis, there was no intersection between the upregulated genes and the red module genes. However, the intersection of the downregulated genes and the red module genes yielded 4 key genes: dopachrome tautomerase (DCT), keratin 3 (KRT3), keratin 76 (KRT76), and FAM3 metabolic regulation signal molecule B (FAM3B). The area under the curve of the diagnostic model constructed by these four genes was 0.963 (CI = 0.913–1.000). The sensitivity was 0.933, and the specificity was 0.923. The diagnostic model was successfully verified in GSE26549 (AUC = 0.745, CI = 0.638–0.851). Compared with the diagnostic models of the previous studies, the diagnostic efficiency of this model was the highest. The small-molecule drugs, selumetinib and benidipine, were selected according to the gene expression profile and showed binding activity when docking with the above molecules. Conclusions This study provides new targets and drugs for OLK. These targets could be used as the key diagnostic molecules for long-term follow-up of OLK. The small-molecule drugs selumetinib and benidipine could be used for the prevention and treatment of OSCC.
Highlights
Oral leukoplakia (OLK) is a potentially malignant disease, with an incidence of 409.2 per 100,000 persons in men and70.0 in women [1]. e pathological manifestations of OLK are various degrees of abnormal epithelial hyperplasia, which eventually progresses to malignant transformation and invades the surrounding tissues [2]
Severe dysplasia is most prone to cancer, so severe dysplasia of OLK is extremely difficult to obtain, which has a certain impact on the results
keratin 3 (KRT3) and keratin 76 (KRT76) are the skeletal components of cells, which are mainly distributed in the skin, mucous membrane, esophagus, and other areas with a high degree of keratinization, and their expression is significantly reduced when cancerous change occurs
Summary
Oral leukoplakia (OLK) is a potentially malignant disease, with an incidence of 409.2 per 100,000 persons in men and70.0 in women [1]. e pathological manifestations of OLK are various degrees of abnormal epithelial hyperplasia, which eventually progresses to malignant transformation and invades the surrounding tissues [2]. Oral leukoplakia (OLK) is a potentially malignant disease, with an incidence of 409.2 per 100,000 persons in men and. E pathological manifestations of OLK are various degrees of abnormal epithelial hyperplasia, which eventually progresses to malignant transformation and invades the surrounding tissues [2]. Photodynamic therapy, microwave therapy, and surgical resection are usually used to prevent cancer development [4]. E clinical manifestations and pathology of patients need to be followed up and monitored. Erefore, early diagnosis is an important means to reduce morbidity and mortality and improve prognosis. It is well known that changes in gene expression usually precede histopathological changes and are closely associated with the progression of cancers [5]. Erefore, abnormal gene expression has become a new perspective for the early diagnosis of OLK It is well known that changes in gene expression usually precede histopathological changes and are closely associated with the progression of cancers [5]. erefore, abnormal gene expression has become a new perspective for the early diagnosis of OLK
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