Tumour architecture shapes polarized epithelial states that predict survival in high-grade serous ovarian cancer
- 1Ottawa Hospital Research Institute
Abstract
High-grade serous ovarian carcinoma (HGSC) is among the most genomically unstable cancers, yet how this diversity relates to malignant-cell states and how they influence treatment response remain unclear. Integrating 1.98 million single-cell transcriptomes across 13 studies, we identify a dominant axis of polarization in malignant secretory cells, from proliferative, progenitor-like (SecA) to quiescent, injury-like (SecB) states that recur across patients and coexist within genetic clones. Spatial profiling of eight whole tumors and tissue microarrays from 378 patients links this polarization to tumor architecture: SecB cells occupy avascular, hypoxic niches, where they adopt HIF/NF-{kappa}B survival programs, exclude lymphocytes, and co-organize with macrophages exhibiting similar glycolytic states. Their localization and enrichment in ascites link SecB to metastasis. SecB predicts poor survival across independent cohorts, but preferential benefit from bevacizumab in the ICON7 trial. Together, these findings reveal shared malignant phenotypes across genomically diverse tumors and highlight their potential to guide treatment selection.
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BibTeX
@misc{nersesian2026tumour,
title = {{Tumour architecture shapes polarized epithelial states that predict survival in high-grade serous ovarian cancer}},
author = {S. Nersesian and J. Abou-Hamad and E. Durocher and G. Akiki and C. Domecq and A. Southworth and H. Deng and Y. Ramos-Valdes and L. Meunier and M. de Ladurantaye and T. Shepherd and D. Provencher and A.-M. Mes Masson and B. Tessier Cloutier and D. P. Cook},
howpublished = {bioRxiv},
year = {2026},
month = may,
doi = {10.64898/2026.05.27.727977},
url = {https://www.biorxiv.org/content/10.64898/2026.05.27.727977v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - Tumour architecture shapes polarized epithelial states that predict survival in high-grade serous ovarian cancer
AU - S. Nersesian
AU - J. Abou-Hamad
AU - E. Durocher
AU - G. Akiki
AU - C. Domecq
AU - A. Southworth
AU - H. Deng
AU - Y. Ramos-Valdes
AU - L. Meunier
AU - M. de Ladurantaye
AU - T. Shepherd
AU - D. Provencher
AU - A.-M. Mes Masson
AU - B. Tessier Cloutier
AU - D. P. Cook
PY - 2026
DA - 2026/05/27
PB - bioRxiv
DO - 10.64898/2026.05.27.727977
UR - https://www.biorxiv.org/content/10.64898/2026.05.27.727977v2
AB - High-grade serous ovarian carcinoma (HGSC) is among the most genomically unstable cancers, yet how this diversity relates to malignant-cell states and how they influence treatment response remain unclear. Integrating 1.98 million single-cell transcriptomes across 13 studies, we identify a dominant axis of polarization in malignant secretory cells, from proliferative, progenitor-like (SecA) to quiescent, injury-like (SecB) states that recur across patients and coexist within genetic clones. Spatial profiling of eight whole tumors and tissue microarrays from 378 patients links this polarization to tumor architecture: SecB cells occupy avascular, hypoxic niches, where they adopt HIF/NF-{kappa}B survival programs, exclude lymphocytes, and co-organize with macrophages exhibiting similar glycolytic states. Their localization and enrichment in ascites link SecB to metastasis. SecB predicts poor survival across independent cohorts, but preferential benefit from bevacizumab in the ICON7 trial. Together, these findings reveal shared malignant phenotypes across genomically diverse tumors and highlight their potential to guide treatment selection.
ER -