Integrated systems biology approach to identify key candidate genes, signaling pathways and therapeutic targets of oral squamous cell carcinoma

Abstract

Background: This research aims to uncover gene signatures associated with oral squamous cell carcinoma (OSCC), the sixth most prevalent cancer globally, constituting about 5% of all malignant tumors. The study focuses on biomarker screening and identifying therapeutic targets, addressing a significant global issue. Materials and Methods: The study involved a comprehensive analysis of publicly available gene expression datasets, namely GSE30784 and GSE74530. The researchers conducted gene ontology (GO) and pathway analyses on genes that displayed differential expression (DEGs). They utilized the Database for Annotation, Visualization, and Integrated Discovery database to accomplish this. The String database also established a protein–protein interaction (PPI) network. This network was visualized through Cytoscape, and further exploration was carried out using Molecular Complex Detection and CytoHubba plugins. These steps aimed to identify crucial hub genes and functional modules. Furthermore, the study investigated transcription factor-gene regulatory networks focusing on the identified hub genes. The researchers employed the Gene Expression Profiling Interactive Analysis 2 tool to evaluate these hub genes’ expression levels and prognostic significance. Results: A comparison between OSCC and normal oral mucosa revealed 1210 DEGs across two databases. The obtained DEG list was cross-referenced with the DisGeNET disease database, identifying 205 potential DEG candidates. These DEGs exhibited enrichments in various biological functions, including angiogenesis, protein binding, focal adhesion, cell surface interactions, and extracellular matrix components. Among the enriched pathways, the interleukin (IL)-17 and tumor necrosis factor signaling pathways related to viral protein interactions showed significant enrichment. Further exploration involved extracting the top five hub genes from intricate PPI networks. These selected hub genes were subsequently verified in clinical samples, paving the way for subsequent in-depth analysis. Conclusion: In the study context, IL-6, chemokine (C-C motif) ligand 2, C-X-C Motif Chemokine Ligand 8, IL-1beta, and prostaglandin-endoperoxide synthase 2 emerged as the leading hub genes linked to the IL-10 signaling pathway in OSCC. These findings offer valuable insights into the potential mechanisms underlying the advancement of OSCC. However, it is essential to underscore that further research must validate these findings conclusively. The study’s outcomes have broadened our understanding of oral cancer’s molecular intricacies by identifying differentially expressed and pivotal hub genes. This newfound knowledge has the potential to catalyze the development of novel biomarkers, thereby enhancing the efficacy of both diagnostic and therapeutic strategies.