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. Altogether, 93 recurrent/metastatic HNSCC patients were enrolled. We performed targeted gene sequencing using Illumina HiSeq-2500 for NGS, and nanostring nCounter^® for mRNA expression; mRNA expression was classified into over- or under-expression groups based on the expression. 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. We calculated a Treatment Benefit Prediction Score (TBPS) to identify suitable drugs. By mapping the high score interaction genes to identify druggable pathways, we found highly related signaling pathways with mutations. Based on the mRNA expression and interaction gene scoring model, several pathways were found to be associated with over- and under-expression. Mutation-based pathways were associated with mRNA under-expressed genes-based pathways. These results suggest that HNSCCs are mainly caused by the loss-of-function mutations. TBPS found several matching drugs such as immune checkpoint inhibitors, EGFR inhibitors, and FGFR inhibitors.

中文翻译：

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头颈部鳞状细胞癌中基于突变和基于表达基因的途径的综合分析

mRNA的过表达或过表达是由遗传改变引起的。基于mRNA表达的全面途径分析与单基因水平突变一样重要。这项研究旨在比较头颈部鳞状细胞癌（HNSCC）中基于突变和mRNA表达的信号传导途径，并将其与潜在的药物或可药物化途径进行匹配。总共纳入了93例复发/转移性HNSCC患者。我们利用Illumina HiSeq-2500为NGS，并nanostring的nCounter进行有针对性的基因测序^®的表达; 基于表达，将mRNA表达分为过表达或欠表达组。我们研究使用CBSJukebox突变和nanostring数据^®系统，这是一个大数据驱动的平台，用于分析可药物途径，基因和蛋白质-蛋白质相互作用。我们计算了治疗效益预测得分（TBPS），以识别合适的药物。通过定位高分相互作用基因以鉴定可药物途径，我们发现了与突变高度相关的信号通路。基于mRNA表达和相互作用基因评分模型，发现了几种与过度表达和表达不足相关的途径。基于突变的途径与mRNA表达不足的基于基因的途径相关。这些结果表明，HNSCCs主要是由功能丧失突变引起的。TBPS发现了几种匹配的药物，例如免疫检查点抑制剂，EGFR抑制剂和FGFR抑制剂。