Epithelial-to-mesenchymal transition signature assessment in colorectal cancer quantifies tumour stromal content rather than true transition

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.