Comprehensive Analysis of Mutation Based and Expressed Genes Based Pathways in Head and Neck Squamous Cell Carcinoma

Background: Over-or under-expression of mRNA results from genetic alterations. Comprehensive pathway analyses based on mRNA expression are as important as single gene level mutations. This study aimed to compare the mutation-and mRNA expression-based signaling pathways in head and neck squamous cell carcinoma (HNSCC), and to match these with potential drug or druggable pathways.Methods: Altogether, 93 recurrent/metastatic HNSCC patients were enrolled. We performed targeted gene sequencing using Agilent 244 customized gene panel for NGS, and nanostring nCounter® for mRNA expression. mRNA expression was classi ed into over-or under expression groups based on the expression levels that showed 2-fold change in tumor compared with non-tumor tissues. We investigated mutational and nanostring data using the CBSJukebox® system, which is a big-data driven platform to analyze druggable pathways, genes, and protein-protein interaction. Analyses were based on 14 databases related to protein interaction, signaling pathways and drugs such as NCBI, Uniprot, KEGG, Biogrid, DIP, HPRD, and Drugbank. High score interaction genes were mapped to investigate druggable pathways. We calculated Treatment Bene t Prediction Score (TBPS) to identify suitable drugs.Results: By mapping the high score interaction genes to identify druggable pathways, we found that highly related signaling pathways with mutation mapping were In uenza A, pathways in cancer, EBV, HPV, HTLV-1 pathways. Based on mRNA expression and interaction gene scoring model, several pathways were found to be associated with over …