Clonal dispersal is associated with tumor heterogeneity and poor prognosis in colorectal cancer
Selami Baglamis, Vivek M. Sheraton, Sanne M. van Neerven, Adrian Logiantara, Lisanne E. Nijman, Laura A. Hageman, Nicolas Léveillé, Clara C. Elbers, Maarten F. Bijlsma, Louis Vermeulen, Przemek M. Krawczyk, Kristiaan J. Lenos
TL;DR
This paper shows that clonal dispersal in colorectal cancer is linked to tumor diversity and worse patient outcomes, offering a new way to predict prognosis.
Contribution
The study introduces a fluorescent cell barcoding method to quantify clonal dispersal and identifies a dispersal gene signature as a prognostic marker.
Findings
Clonal dispersal is correlated with epithelial-mesenchymal transition and CMS4 signaling pathways.
A dispersal gene signature is a robust predictor of poor prognosis and recurrence in CRC.
Clonal dispersal varies across CRC models and is associated with intratumor heterogeneity.
Abstract
Clonal dispersal, resulting from the intermingling of tumor cell subpopulations, is thought to be a key driver of tumor heterogeneity. Despite advances in spatial modeling of cancer biology, quantification of clonal dispersal has been challenging. This study introduces a straightforward method, relying on fluorescent cell barcoding, to quantify clonal dispersal in various in vitro and in vivo models of colorectal cancer (CRC). Our approach allows for precise localization of clones and uncovering the degree of clonal mixing across different CRC models. Our findings suggest that clonal dispersal is correlated with the expression of genes involved in epithelial-mesenchymal transition and CMS4-related signaling pathways. We further identify a dispersal gene signature, associated with intratumor heterogeneity, which is a robust clinical predictor of poor prognosis and recurrence in CRC,…
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Taxonomy
TopicsColorectal Cancer Treatments and Studies · Colorectal Cancer Screening and Detection · Cancer, Lipids, and Metabolism