Malignant and stromal partial EMT programmes and cetuximab outcome in head and neck cancer

Partial epithelial-to-mesenchymal transition (pEMT) was observed in malignant cells of head and neck squamous cell carcinoma during single-cell analyses, but is typically measured in bulk tumours. Three single-cell datasets revealed that malignant cells expressed laminin-332 and hemidesmosome genes, while fibroblasts expressed fibrillar collagens and vimentin.

In bulk tumours, the stromal arm dominated co-expression, resulting in standard pEMT scores primarily reflecting stroma. Researchers developed a classifier trained on single cells to recover the malignant arm and a 12-gene core. In a study of 40 patients treated with platinum and cetuximab, the malignant arm showed higher scores in those with a longer progression-free survival, with an area under the curve of 0.78 and 0.82.

The stromal arm did not correlate with progression-free survival. The malignant arm was closely linked to the Basal subtype, achieving scores as good or better than patients with these characteristics in two xenograft panels. Bulk pEMT scores should be interpreted based on the cell of origin.