eIFs as novel biomarkers in head and neck squamous cell carcinoma
Kurzbeschreibung
The present invention is biomarkers that enable clinical diagnosis. By determining the eukaryotic initiation factors, a survival prognosis for those affected by head and neck squamous cell carcinomas can be derived.
Beschreibung/Hintergrund
Head and Neck Squamous Cell Carcinoma (HNSCC) develops in the mucosa of the oral cavity of the pharynx, larynx and paranasal sinuses. Every year over 68 000 patients are diagnosed new with HNSCC worldwide. The mortality rate is estimated at 40-50 %. HNSCC is characterized by extraordinary intra- and inter-tumoral genetic heterogeneity, which might explain the different reactions of patients to HNSCC therapy. This underlines the need to provide therapies for the treatment of HNSCC.
Lösung
The inventors examined the performance of eukaryotic translation initiation factors (eIFs) as biomarkers in Head and Neck Squamous Cell Carcinoma. The inventors examined the mRNA expression data of 279 HNSCC patients and found that patients with high expression of all subunits of eIF2 and low expression of the eIF2AK1/HRI kinase showed a lower overall survival. Further, they found that an upregulation of all subunits of eIF2 and a downregulation of eIF2AK1/HRI compared to controls is indicative for HNSCC. The inventors also found that the treatment with eIF2S1/eIF2α inhibitor Salubrinal leads to a reduction of cell viability in vitro and in 3D organoids experiments. Thus, eIF2α eIF is useful both as a molecular marker and as a therapeutic target in HNSCC.