Prognostic value of hypoxia-responsive gene expression profile in patients diagnosed with head and neck squamous cell carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a disease associated with a severe mortality and high risk of distant metastasis and local recurrence. Currently, surgery and radiotherapy are the main treatment modes, however, therapeutic efficacy of radiotherapy is linked to tumor resistance. Hypoxia has been shown to affect outcome of radiotherapy in HNSCC patients. The aim of this study was to verify the expression of the previously identified hypoxia-responsive genes (CA9, CASP14, LOX, GLUT3, SERPINE1, AREG, EREG, CCNB1 and KIF14) in HNSCC patient material as well as assess their prognostic potential. Tumor biopsies obtained before start of radiotherapy from 32 HNSCC patients classified as responders or non-responders were investigated in this study. The mRNA expression was quantified using RT-qPCR. The mRNA expression of CA9, SERPINE1 and KIF14 was significantly higher in the analyzed patient material compared with the non-cancerous oral tissue. Moreover, the KIF14 mRNA expression was significantly higher in the responder group compared to non-responders. Further studies demonstrated that knockdown of KIF14 reverses its radiosensitizing capability. Additionally, low expression of KIF14 mRNA correlated with significantly shorter OS (overall survival). In conclusion, our results suggest that KIF14 might be a useful prognostic and predictive marker in HNSCC.