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

NOTCH1 胞内结构域和肿瘤微环境作为 HNSCC 的预后标志物

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作者:Benedikt Schmidl, Michael Siegl, Melanie Boxberg, Fabian Stögbauer, Daniel Jira, Christof Winter, Leonhard Stark, Anja Pickhard, Barbara Wollenberg, Markus Wirth

Background

NOTCH1 is the second most common mutated gene in whole-exome sequencing of HNSCC. The

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.

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.

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