Malignant and stromal partial EMT programmes and cetuximab outcome in head and neck cancer
- 1Milner Therapeutics Institute, University of Cambridge, Cambridge, United Kingdom
Abstract
Partial epithelial-to-mesenchymal transition (pEMT) was defined in single malignant cells of head and neck squamous cell carcinoma but is usually scored in bulk tumours. In three single-cell datasets, its laminin-332 and hemidesmosome genes were expressed by malignant cells (the malignant arm) and its fibrillar collagens and vimentin by fibroblasts (the stromal arm). In bulk tumours the stromal arm dominated co-expression, so standard pEMT scores mainly measure stroma. We recovered the malignant arm with a classifier trained on single cells and a 12-gene core. In 40 patients treated with platinum and cetuximab, both malignant measures were higher in those with long progression-free survival (area under the curve 0.78 and 0.82), and the stromal arm was not. The malignant arm was inseparable from the Basal subtype, whose score did as well or better in these patients (0.93) and in two xenograft panels. Bulk pEMT scores should be read by cell of origin.
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BibTeX
@misc{alkhatib2026malignant,
title = {{Malignant and stromal partial EMT programmes and cetuximab outcome in head and neck cancer}},
author = {D. Z. R. Alkhatib and S. Lunetto and P. Chakraborty and M. K. Jolly and M. P. Philpott and A. Biddle and G. Youssef and N. Han},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.757840},
url = {https://www.biorxiv.org/content/10.64898/2026.10.09.757840v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Malignant and stromal partial EMT programmes and cetuximab outcome in head and neck cancer
AU - D. Z. R. Alkhatib
AU - S. Lunetto
AU - P. Chakraborty
AU - M. K. Jolly
AU - M. P. Philpott
AU - A. Biddle
AU - G. Youssef
AU - N. Han
PY - 2026
DA - 2026/10/09
PB - bioRxiv
DO - 10.64898/2026.10.09.757840
UR - https://www.biorxiv.org/content/10.64898/2026.10.09.757840v1
AB - Partial epithelial-to-mesenchymal transition (pEMT) was defined in single malignant cells of head and neck squamous cell carcinoma but is usually scored in bulk tumours. In three single-cell datasets, its laminin-332 and hemidesmosome genes were expressed by malignant cells (the malignant arm) and its fibrillar collagens and vimentin by fibroblasts (the stromal arm). In bulk tumours the stromal arm dominated co-expression, so standard pEMT scores mainly measure stroma. We recovered the malignant arm with a classifier trained on single cells and a 12-gene core. In 40 patients treated with platinum and cetuximab, both malignant measures were higher in those with long progression-free survival (area under the curve 0.78 and 0.82), and the stromal arm was not. The malignant arm was inseparable from the Basal subtype, whose score did as well or better in these patients (0.93) and in two xenograft panels. Bulk pEMT scores should be read by cell of origin.
ER -