Expressional analysis of disease-relevant signalling-pathways in primary tumours and metastasis of head and neck cancers

Abstract Head and neck squamous cell carcinoma (HNSCC) often metastasize to lymph nodes resulting in poor prognosis for patients. Unfortunately, the underlying molecular mechanisms contributing to tumour aggressiveness, recurrences, and metastasis are still not fully understood. However, such knowle...

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Autores principales:	Dorothee Goesswein, Negusse Habtemichael, Aslihan Gerhold-Ay, Johanna Mazur, Désirée Wünsch, Shirley K. Knauer, Julian Künzel, Christoph Matthias, Sebastian Strieth, Roland H. Stauber
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d83d6074615346329b0cdcf3b566e10a
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spelling	oai:doaj.org-article:d83d6074615346329b0cdcf3b566e10a2021-12-02T12:31:56ZExpressional analysis of disease-relevant signalling-pathways in primary tumours and metastasis of head and neck cancers10.1038/s41598-018-25512-72045-2322https://doaj.org/article/d83d6074615346329b0cdcf3b566e10a2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25512-7https://doaj.org/toc/2045-2322Abstract Head and neck squamous cell carcinoma (HNSCC) often metastasize to lymph nodes resulting in poor prognosis for patients. Unfortunately, the underlying molecular mechanisms contributing to tumour aggressiveness, recurrences, and metastasis are still not fully understood. However, such knowledge is key to identify biomarkers and drug targets to improve prognosis and treatments. Consequently, we performed genome-wide expression profiling of 15 primary HNSSCs compared to corresponding lymph node metastases and non-malignant tissue of the same patient. Differentially expressed genes were bioinformatically exploited applying stringent filter criteria, allowing the discrimination between normal mucosa, primary tumours, and metastases. Signalling networks involved in invasion contain remodelling of the extracellular matrix, hypoxia-induced transcriptional modulation, and the recruitment of cancer associated fibroblasts, ultimately converging into a broad activation of PI3K/AKT-signalling pathway in lymph node metastasis. Notably, when we compared the diagnostic and prognostic value of sequencing data with our expression analysis significant differences were uncovered concerning the expression of the receptor tyrosine kinases EGFR and ERBB2, as well as other oncogenic regulators. Particularly, upregulated receptor tyrosine kinase combinations for individual patients varied, implying potential compensatory and resistance mechanisms against specific targeted therapies. Collectively, we here provide unique transcriptional profiles for disease predictions and comprehensively analyse involved signalling pathways in advanced HNSCC.Dorothee GoessweinNegusse HabtemichaelAslihan Gerhold-AyJohanna MazurDésirée WünschShirley K. KnauerJulian KünzelChristoph MatthiasSebastian StriethRoland H. StauberNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dorothee Goesswein Negusse Habtemichael Aslihan Gerhold-Ay Johanna Mazur Désirée Wünsch Shirley K. Knauer Julian Künzel Christoph Matthias Sebastian Strieth Roland H. Stauber Expressional analysis of disease-relevant signalling-pathways in primary tumours and metastasis of head and neck cancers
description	Abstract Head and neck squamous cell carcinoma (HNSCC) often metastasize to lymph nodes resulting in poor prognosis for patients. Unfortunately, the underlying molecular mechanisms contributing to tumour aggressiveness, recurrences, and metastasis are still not fully understood. However, such knowledge is key to identify biomarkers and drug targets to improve prognosis and treatments. Consequently, we performed genome-wide expression profiling of 15 primary HNSSCs compared to corresponding lymph node metastases and non-malignant tissue of the same patient. Differentially expressed genes were bioinformatically exploited applying stringent filter criteria, allowing the discrimination between normal mucosa, primary tumours, and metastases. Signalling networks involved in invasion contain remodelling of the extracellular matrix, hypoxia-induced transcriptional modulation, and the recruitment of cancer associated fibroblasts, ultimately converging into a broad activation of PI3K/AKT-signalling pathway in lymph node metastasis. Notably, when we compared the diagnostic and prognostic value of sequencing data with our expression analysis significant differences were uncovered concerning the expression of the receptor tyrosine kinases EGFR and ERBB2, as well as other oncogenic regulators. Particularly, upregulated receptor tyrosine kinase combinations for individual patients varied, implying potential compensatory and resistance mechanisms against specific targeted therapies. Collectively, we here provide unique transcriptional profiles for disease predictions and comprehensively analyse involved signalling pathways in advanced HNSCC.
format	article
author	Dorothee Goesswein Negusse Habtemichael Aslihan Gerhold-Ay Johanna Mazur Désirée Wünsch Shirley K. Knauer Julian Künzel Christoph Matthias Sebastian Strieth Roland H. Stauber
author_facet	Dorothee Goesswein Negusse Habtemichael Aslihan Gerhold-Ay Johanna Mazur Désirée Wünsch Shirley K. Knauer Julian Künzel Christoph Matthias Sebastian Strieth Roland H. Stauber
author_sort	Dorothee Goesswein
title	Expressional analysis of disease-relevant signalling-pathways in primary tumours and metastasis of head and neck cancers
title_short	Expressional analysis of disease-relevant signalling-pathways in primary tumours and metastasis of head and neck cancers
title_full	Expressional analysis of disease-relevant signalling-pathways in primary tumours and metastasis of head and neck cancers
title_fullStr	Expressional analysis of disease-relevant signalling-pathways in primary tumours and metastasis of head and neck cancers
title_full_unstemmed	Expressional analysis of disease-relevant signalling-pathways in primary tumours and metastasis of head and neck cancers
title_sort	expressional analysis of disease-relevant signalling-pathways in primary tumours and metastasis of head and neck cancers
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/d83d6074615346329b0cdcf3b566e10a
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Expressional analysis of disease-relevant signalling-pathways in primary tumours and metastasis of head and neck cancers

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