Wound-like tumor periphery in human breast cancer predicts a convergent drug nonresponse

Li, L.; Liao, X.; Fu, F.; Xi, G.; Kang, D.; He, J.; Guo, W.; Qiu, L.; Han, Z.; Wang, X.; Zhan, Q.; You, S.; Chen, J.; Wang, C.; Boppart, S. A.; Tu, H.

doi:10.1101/2021.11.02.467008

bioRxiv · 10.1101/2021.11.02.467008

Wound-like tumor periphery in human breast cancer predicts a convergent drug nonresponse

Li, L.·Liao, X.·Fu, F.·Xi, G.·Kang, D.·He, J.·Guo, W.·Qiu, L.·Han, Z.·Wang, X.·Zhan, Q.·You, S.·Chen, J.·Wang, C.·Boppart, S. A.·Tu, H.

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Abstract

A significant portion of breast cancer patients are nonresponsive to well-established drugs and destined for a poor outcome regardless of molecular subtype. Although several (multiparameter) molecular markers have predicted their resistance to some of these drugs, profound uniparameter markers predictive of a convergent nonresponse to all these drugs remain elusive. We employ co-registered standard-multiphoton histology to representatively sample a few peripheral niches of the primary tumor, so that hundreds of patients can be stratified with either a wound-like or non-wound tumor periphery. With no fitting variable, this simple uniparameter morphological marker is: (a) highly sensitive and specific to predict a multidrug-nonresponsive phenotype that accounts for the majority of recurrence or death, independent of the molecular subtype or related adjuvant drug selection, clinical endpoint (disease-free versus overall survival), and hosting medical center; (b) robust against intratumor heterogeneity and valid at the earliest clinicopathological stage; and (c) dominant in predicting prognosis in the context of routine clinicopathological markers. Considering the mechanistic link between a wound-like extracellular matrix and a microenvironment supporting migratory or mesenchymal tumor cells, we attribute these unusual capabilities to an epithelial-mesenchymal transition nature of the morphological marker long sought after by pathologists.

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Li, L., Liao, X., Fu, F., Xi, G., Kang, D., He, J., Guo, W., Qiu, L., Han, Z., Wang, X., Zhan, Q., You, S., Chen, J., Wang, C., Boppart, S. A., Tu, H.. 2021-11-04. Wound-like tumor periphery in human breast cancer predicts a convergent drug nonresponse. https://doi.org/10.1101/2021.11.02.467008

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