Expressional analysis of disease-relevant signalling-pathways in primary tumours and metastasis of head and neck cancers.
Dorothee GößweinNegusse HabtemichaelAslihan Gerhold-AyJohanna MazurDésirée WünschShirley K KnauerJulian KünzelChristoph MatthiasSebastian StriethRoland H StauberPublished in: Scientific reports (2018)
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.
Keyphrases
- poor prognosis
- lymph node
- tyrosine kinase
- genome wide
- extracellular matrix
- end stage renal disease
- lymph node metastasis
- pi k akt
- long non coding rna
- ejection fraction
- transcription factor
- chronic kidney disease
- epidermal growth factor receptor
- gene expression
- newly diagnosed
- signaling pathway
- small cell lung cancer
- dna methylation
- squamous cell carcinoma
- healthcare
- peritoneal dialysis
- prognostic factors
- emergency department
- oxidative stress
- machine learning
- radiation therapy
- artificial intelligence
- young adults
- big data
- drug induced
- heat stress
- electronic health record
- cell cycle arrest