A novel panel of biomarkers predicts radioresistance in patients with squamous cell carcinoma of the head and neck

Abstract Purpose Global gene expression analysis was performed on pre-treatment biopsies from patients with squamous cell carcinoma of the head and neck (SCCHN) to discover biomarkers that can predict outcome of radiation based therapy. Methods We initially evaluated RNA expression using cDNA microa...

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Published in:	European journal of cancer (1990) Vol. 50; no. 3; pp. 570 - 581
Main Authors:	Akervall, Jan, Nandalur, Sirisha, Zhang, Jacob, Qian, Chao-Nan, Goldstein, Neal, Gyllerup, Paulina, Gardinger, Ylva, Alm, Jens, Lorenc, Katarina, Nilsson, Karolina, Resau, James, Wilson, George, Teh, Bin
Format:	Journal Article
Language:	English
Published:	Kidlington Elsevier Ltd 01-02-2014 Elsevier
Subjects:	Adult Aged Aged, 80 and over Biological and medical sciences Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism c-MET Cancer and Oncology Cancer och onkologi Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - radiotherapy Clinical Medicine Female Gene Expression Profiling Head and neck cancer Head and Neck Neoplasms - genetics Head and Neck Neoplasms - metabolism Head and Neck Neoplasms - radiotherapy Hematology, Oncology and Palliative Medicine Humans Klinisk medicin Male Medical and Health Sciences Medical sciences Medicin och hälsovetenskap Middle Aged Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Oligonucleotide Array Sequence Analysis Pharmacology. Drug treatments Predictive biomarkers Radiation Tolerance Radio-resistance Squamous cell carcinoma Squamous Cell Carcinoma of Head and Neck Tumors YAP-1 YAP-1 Head and neck cancer Squamous cell carcinoma c-MET Radio-resistance Predictive biomarkers Human Skin disease Treatment resistance Basal cell carcinoma Prediction Biological marker Malignant tumor Radiotherapy Cancerology Treatment C-Onc gene ENT disease Head and neck squamous cell carcinoma Predictive factor Protooncogene Cancer
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Summary:	Abstract Purpose Global gene expression analysis was performed on pre-treatment biopsies from patients with squamous cell carcinoma of the head and neck (SCCHN) to discover biomarkers that can predict outcome of radiation based therapy. Methods We initially evaluated RNA expression using cDNA microarray analysis of 38 patients that received radiotherapy (RT). The five strongest candidates ( VEGF , BCL-2 , CLAUDIN-4 , YAP-1 and c-MET ) were then analysed in pre-treatment biopsies in a second group of 86 patients who received radiation based treatment using immunohistochemical staining (IHC), prepared by tissue microarray. Results In the first population, 13 of 38 (34%) had no (NR) or partial response (PR) to RT. cDNA microarrays revealed 60 genes that were linked to response to therapy. In the second series, 12 of 86 patients (14%) experienced NR or PR to CRT. Cause specific survival (CSS) and recurrence free survival (RFS) at 2 years was 85% and 90% and at 3 years 81% and 84%, respectively. Biomarkers predictive for NR/PR were increased expression of vascular endothelial growth factor (VEGF) ( p = 0.02), Yes-associated protein (YAP-1) ( p < 0.01), CLAUDIN-4 ( p < 0.01), c-MET ( p < 0.01) and BCL-2 ( p = 0.02). Biomarkers predictive of poor RFS were YAP-1 ( p = 0.01) and BCL-2 ( p < 0.01). Biomarkers predictive of poor CSS were YAP-1 ( p = 0.04), VEGF ( p = 0.03) and CLAUDIN-4 ( p = 0.03). Furthermore, when YAP-1 and c-MET expression levels were combined the prediction of radio-resistance was increased. Conclusion All five biomarkers were predictive of poor response to radiation based therapy. In particular, YAP-1 and c-MET have synergistic power and could be used to make treatment decisions.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0959-8049 1879-0852 1879-0852
DOI:	10.1016/j.ejca.2013.11.007