NOTCH1 Intracellular Domain and the Tumor Microenvironment as Prognostic Markers in HNSCC

Simple Summary In the head and neck, a large proportion of squamous cell carcinoma demonstrate a mutation of the NOTCH1 gene. The aim of this project was to investigate the role of NOTCH1 and immunological characteristics and highlight a potential rationale for therapy. We found that a high expression of NOTCH1 intracellular domain in these patients is associated with reduced overall survival. In vitro experiments additionally showed a reduction of migration and proliferation of cancer cells when NOTCH1 was knocked down. NOTCH1 is, therefore, most likely involved in migration and proliferation of head and neck squamous cell carcinoma and is a prognostic marker in these patients. (1) Background: NOTCH1 is the second most common mutated gene in whole-exome sequencing of HNSCC. The aim of this project was to gain further insight into the relevance of NOTCH1 in HNSCC, potentially establishing NOTCH1 as a prognostic marker or therapeutic target; (2) Methods: NOTCH1 was silenced via RNA interference in six HNSCC cell lines and the impact was evaluated in migration and proliferation assays. Subsequently, the protein expression of NOTCH1 intracellular domain (NICD) and NOTCH1 mRNA expression were examined in 70 oropharyngeal squamous cell cancer tissue samples. Lastly, the NICD expression was compared with the local infiltration of lymphocytes, measured with the immunoscore; (3) Results: Knockdown of NOTCH1 decreased migration and proliferation. A high NICD expression was associated with lower OS. A high immunoscore resulted in significantly better OS. NICD expression was independent of the immunoscore and as a whole differentiated three distinct prognostic groups; (4) Conclusions: These data suggest that NOTCH1 is involved in migration and proliferation of HNSCC cell lines. In vivo, NICD expression was associated with overall survival and could, therefore, be used as a prognostic marker. NICD expression differs from NOTCH1 mRNA levels, potentially explaining the previously suggested bimodal role as an oncogene and tumor suppressor in HNSCC.

Automated summary

The NOTCH1 gene mutation is common in squamous cell carcinoma in the head and neck. This study found that a high expression of NOTCH1 is associated with reduced survival in these patients. In vitro experiments showed that knocking down NOTCH1 reduces migration and proliferation of cancer cells. This suggests that NOTCH1 is involved in the migration and proliferation of head and neck squamous cell carcinoma and could be a prognostic marker.