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bioRxiv · 10.1101/2024.11.07.622481

Morpho-molecular features of Epithelial Mesenchymal Transition associate with clinical outcome in patients with rectal cancer

Gwerder, M.·Demir, C. S.·Williams, H. L.·Lugli, A.·Martinez, C. G.·Kowal, j.·Khan, A.·Kirchner, P.·Koessler, T.·Berger, M. D.·Weigert, M.·Zlobec, I.
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Abstract

In rectal cancer, where part of the patients undergoes chemoradiotherapy, there is a need for improved pretreatment biomarkers applicable to biopsies. Tumor budding (TB) is a biomarker used in colon cancer, and due to its link to epithelial-mesenchymal transition (EMT), is hypothesized to be a potential marker for therapy resistance. Assessment of the utility of tumor buds in rectal biopsies is challenging due to their rarity. As EMT-related processes are also seen in other morphological features beyond tumor buds, we investigated EMT in tumor tissue including morphological features such as tumor cluster size and fibril-like structures. To do so, we leveraged a cohort of colon cancer whole-slide images and another cohort consisting of rectal cancer biopsies, visualized using hyperplex immunofluorescence to identify tumor and EMT-associated proteins. We built a custom image analysis pipeline to detect and segment tumor buds and other morphological features and correlated them with molecular expression intensities. We found strong correlations of EMT up-regulation and morphological transition states, both at the invasive margin and the tumor center. We furthermore observed a link between morpho-molecular transitions and histological growth patterns, which in turn can inform novel biomarkers. Finally, quantification of these morpho-molecular transition states in rectal biopsies showed their impact on survival after neoadjuvant chemoradiotherapy.

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Gwerder, M., Demir, C. S., Williams, H. L., Lugli, A., Martinez, C. G., Kowal, j., Khan, A., Kirchner, P., Koessler, T., Berger, M. D., Weigert, M., Zlobec, I.. 2024-11-10. Morpho-molecular features of Epithelial Mesenchymal Transition associate with clinical outcome in patients with rectal cancer. https://doi.org/10.1101/2024.11.07.622481

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