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

2020 ◽  
Author(s):  
Bhumsuk Keam ◽  
Jin Young Park ◽  
Jinpyo Kim ◽  
Gun Do Kim ◽  
Yunsuk Yu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Big Data ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Squamous Cell ◽  
Protein Interaction ◽  
Genetic Alterations ◽  
Neck Squamous Cell Carcinoma

Abstract 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 classified 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 Benefit 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 Influenza 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- and under-expression. Comparison between mutation-based pathway and over-/under-expressed genes-based pathways, we observed that 19.8% of NGS based pathways matched with mRNA over-expressed genes-based pathways, and 43.2% of NGS based pathways consist with mRNA under-expressed genes-based pathways. TBPS found several matching drugs such as immune checkpoint inhibitors, EGFR inhibitors, and FGFR inhibitors.Conclusions: Mutation-based pathway was associated with mRNA under-expressed genes-based pathway. These results suggest that HNSCCs are mainly caused by the loss-of-function mutations. However, big data based platform for druggable pathway can find potential matching drugs.

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

Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 792
Author(s):  
Bhumsuk Keam ◽  
Jin Young Park ◽  
Jinpyo Kim ◽  
Gun Do Kim ◽  
Yunsuk Yu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Squamous Cell ◽  
Checkpoint Inhibitors ◽  
Single Gene ◽  
Genetic Alterations ◽  
Neck Squamous Cell Carcinoma

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.

scholarly journals A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Aneesha Radhakrishnan ◽  
Vishalakshi Nanjappa ◽  
Remya Raja ◽  
Gajanan Sathe ◽  
Vinuth N. Puttamallesh ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Squamous Cell ◽  
Therapeutic Target ◽  
Neck Squamous Cell Carcinoma ◽  
Dual Specificity ◽  
Hnscc Cell

Abstract Despite advances in clinical management, 5-year survival rate in patients with late-stage head and neck squamous cell carcinoma (HNSCC) has not improved significantly over the past decade. Targeted therapies have emerged as one of the most promising approaches to treat several malignancies. Though tyrosine phosphorylation accounts for a minority of total phosphorylation, it is critical for activation of signaling pathways and plays a significant role in driving cancers. To identify activated tyrosine kinase signaling pathways in HNSCC, we compared the phosphotyrosine profiles of a panel of HNSCC cell lines to a normal oral keratinocyte cell line. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Tyr-321 in all HNSCC cell lines. Inhibition of DYRK1A resulted in an increased apoptosis and decrease in invasion and colony formation ability of HNSCC cell lines. Further, administration of the small molecular inhibitor against DYRK1A in mice bearing HNSCC xenograft tumors induced regression of tumor growth. Immunohistochemical labeling of DYRK1A in primary tumor tissues using tissue microarrays revealed strong to moderate staining of DYRK1A in 97.5% (39/40) of HNSCC tissues analyzed. Taken together our results suggest that DYRK1A could be a novel therapeutic target in HNSCC.

scholarly journals Search for mutations in signaling pathways in head and neck squamous cell carcinoma

2013 ◽  
Vol 30 (1) ◽  
pp. 334-340 ◽  
Author(s):  
THAIS GULIM DE CARVALHO ◽  
ANA CAROLINA DE CARVALHO ◽  
DANIELLE CALHEIROS CAMPELO MAIA ◽  
JULIANA KAORI OGAWA ◽  
ANDRE LOPES CARVALHO ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Signaling Pathways ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma

scholarly journals Epigenetic and Genetic Alterations Affect the WWOX Gene in Head and Neck Squamous Cell Carcinoma

PLoS ONE ◽  
2015 ◽  
Vol 10 (1) ◽  
pp. e0115353 ◽  
Author(s):  
Seda Ekizoglu ◽  
Pelin Bulut ◽  
Emin Karaman ◽  
Erkan Kilic ◽  
Nur Buyru
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Genetic Alterations ◽  
Neck Squamous Cell Carcinoma ◽  
Wwox Gene

The genomic architechtures of tumor-adjacent tissues, plasma and saliva reveal evolutionary underpinnings of relapse in head and neck squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18046-e18046
Author(s):  
Ping Wu ◽  
Zicheng Yu ◽  
Chubo Xie ◽  
Ling Yang ◽  
Xuefeng Xia ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Evolutionary Relationship ◽  
Genetic Alterations ◽  
Neck Squamous Cell Carcinoma ◽  
Liquid Biopsies ◽  
Primary Tumors ◽  
Dismal Prognosis

e18046 Background: Head and neck squamous cell carcinoma (HNSCC) is characterized by dismal prognosis, nonetheless limited studies have unveiled the mechanisms underlying HNSCC relapse. Methods: Next-generation sequencing 1 5 was performed to identify somatic mutations in 188 matched samples including primary tumors, tumor adjacent tissues (TATs), pre- and post-operative plasma, saliva and peripheral blood lymphocytes (PBLs) from 27 patients. Evolutionary relationship between TATs and tumors were analyzed. The dynamic changes of tumor- and TAT-specific mutations in liquid biopsies were monitored together with survival analysis. Results: Alterations were detected in 27/27 and 19/26 tumors and TATs respectively. TP53 was the most prevalent genes mutated in TATs. Some TATs shared mutations with primary tumors, while some other TATs were evolutionarily unrelated to tumors. Notably, TP53 mutations in TATs are stringently associated with premalignant transformation and indicative of worse survival (HR=14.01). TAT-specific mutations were also detected in pre- and/or post-operative liquid biopsies, and indicative of disease relapse. Conclusions: TATs might undergo the processes of premalignant transformation, tumorigenesis, and eventually relapse by either inheriting tumorigenic mutations from ancestral clones where tumor originated or gaining private mutations independent to primary tumor. Detection of tumor- and/or TAT-specific genetic alterations in post-operative biopsies shows profound potential in prognostic use.

scholarly journals Elevated gastrin-releasing peptide receptor mRNA expression in buccal mucosa: Association with head and neck squamous cell carcinoma

Head & Neck ◽  
2012 ◽  
Vol 35 (2) ◽  
pp. 270-279 ◽  
Author(s):  
Ann Marie Egloff ◽  
Xuwan Liu ◽  
Autumn L. Gaither Davis ◽  
Brian K. Trevelline ◽  
Marike Vuga ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Mrna Expression ◽  
Squamous Cell ◽  
Buccal Mucosa ◽  
Neck Squamous Cell Carcinoma ◽  
Peptide Receptor ◽  
Gastrin Releasing Peptide ◽  
Receptor Mrna
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