Analysis of cell proliferation and tissue remodelling uncovers a KLF4 activity score associated with poor prognosis in colorectal cancer

Halim, S., Markert, E. K. and Vazquez, A. (2018) Analysis of cell proliferation and tissue remodelling uncovers a KLF4 activity score associated with poor prognosis in colorectal cancer. British Journal of Cancer, 119(7), pp. 855-863. (doi: 10.1038/s41416-018-0253-0) (PMID:30287917)

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Human cancers can be classified based on gene signatures quantifying the degree of cell proliferation and tissue remodelling (PR). However, the specific factors that drive the increased tissue remodelling in tumours are not fully understood. Here we address this question using colorectal cancer as a case study. We reanalysed a reported cohort of colorectal cancer patients. The patients were stratified based on gene signatures of cell proliferation and tissue remodelling. Putative transcription factors activity was inferred using gene expression profiles and annotations of transcription factor targets as input. We demonstrate that the PR classification performs better than the currently adopted consensus molecular subtyping (CMS). Although CMS classification differentiates patients with a mesenchymal signature, it cannot distinguish the remaining patients based on survival. We demonstrate that the missing factor is cell proliferation, which is indicative of good prognosis. We also uncover a KLF4 transcription factor activity score associated with the tissue remodelling gene signature. We further show that the KLF4 activity score is significantly higher in colorectal tumours with predicted infiltration of cells from the myeloid lineage. The KLF4 activity score is associated with tissue remodelling, myeloid cell infiltration and poor prognosis in colorectal cancer.

Item Type:Articles
Additional Information:This work was supported by Cancer Research UK C596/A21140. This project has received funding from the European Unions Horizon 2020 research and innovation programme MSCA-RISE-2016 under grant agreement No. 734439 INFERNET.
Glasgow Author(s) Enlighten ID:Markert, Dr Elke and Halim, Silvia and Vazquez, Alexei
Authors: Halim, S., Markert, E. K., and Vazquez, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:British Journal of Cancer
Publisher:Springer Nature
ISSN (Online):1532-1827
Published Online:05 October 2018

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