Partial epithelial-to-mesenchymal transition is prognostic and associates with Slug in head and neck cancer
Schinke, H.; Pan, M.; Akyol, M.; Kranz, G.; Libl, D.; Simon, F.; Canis, M.; Baumeister, P.; Gires, O.
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Therapy resistance leading to local recurrence and metastases remains highly problematic in head and neck squamous cell carcinomas (HNSCC). Single cell RNA-sequencing defined a partial epithelial-to-mesenchymal transition (p-EMT) signature associated with metastases in HNSCC. However, the prognostic value of the p-EMT signature and potential drivers of p-EMT in HNSCC remain unclear. Here, single sample scoring of molecular phenotypes (Singscoring) served to establish clinical p-EMT-Singscores that were significantly associated with nodal metastases and predicted overall survival in two independent HNSCC cohorts. p-EMT-Singscores correlated most strongly with EMT transcription factor (EMT-TF) Slug. In vitro, Slug promoted p-EMT, enhanced invasion, and resistance to irradiation. In patients, Slug protein levels in tumors predicted disease-free survival and its peripheral expression at the interphase to tumor-microenvironment was significantly increased in recurring patients. Thus, p-EMT represents a novel clinical risk-predictor that impacts on HNSCC patients outcome and is partly controlled by Slug.
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