RESUMO
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.
