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Epithelial‐to‐mesenchymal transition signature assessment in colorectal cancer quantifies tumour stromal content rather than true transition
Author(s) -
McCorry Amy MB,
Loughrey Maurice B,
Longley Daniel B,
Lawler Mark,
Dunne Philip D
Publication year - 2018
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5155
Subject(s) - epithelial–mesenchymal transition , stromal cell , subtyping , transition (genetics) , in silico , mesenchymal stem cell , biology , cancer research , pathology , pathological , cancer , colorectal cancer , microrna , oncology , medicine , microbiology and biotechnology , gene , genetics , computer science , programming language
Abstract The process of epithelial‐to‐mesenchymal transition (EMT) in cancer is a well‐described process whereby epithelial tumour cells undergo molecular/phenotypic changes and transition to a mesenchymal biology. To aid in the transcriptional characterisation of this process, gene expression signatures have been developed that attribute a relative EMT score to samples in a given cohort. We demonstrate how such EMT signatures can identify epithelial cell line models with high levels of transition but also highlight that, unsurprisingly, fibroblast cell lines, which are inherently mesenchymal, have a higher EMT score relative to any epithelial cell line studied. In line with these data, we demonstrate how increased tumour stromal composition, and reduced epithelial cellularity, significantly correlates with increasing EMT signature score, which is evident using either in silico subtyping analysis ( p < 0.00001) or in situ histopathological characterisation ( p < 0.001). Considered together, these results reinforce the importance not only of interdisciplinary research to correctly define the nature of EMT biology but also the requirement for a cadre of multidisciplinary researchers who can analyse and interpret the underlying pathological, bioinformatic and molecular data that are essential for advancing our understanding of the malignant process. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.