Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients

By T. Tan, Q. H. Miow, Yoshio Miki, Tetsuo Noda, S. Mori, R. Huang, J. P. Thiery. EMBO Molecular Medicine, 2014

674 citations recorded by the source corpus.

Epithelial‐mesenchymal transition (EMT) is a reversible and dynamic process hypothesized to be co‐opted by carcinoma during invasion and metastasis. Yet, there is still no quantitative measure to assess the interplay between EMT and cancer progression. Here, we derived a method for universal EMT scoring from cancer‐specific transcriptomic EMT signatures of ovarian, breast, bladder, lung, colorectal and gastric cancers. We show that EMT scoring exhibits good correlation with previously published, cancer‐specific EMT signatures. This universal and quantitative EMT scoring was used to establish an EMT spectrum across various cancers, with good correlation noted between cell lines and tumours. We show correlations between EMT and poorer disease‐free survival in ovarian and colorectal, but not breast, carcinomas, despite previous notions. Importantly, we found distinct responses between epithelial‐ and mesenchymal‐like ovarian cancers to therapeutic regimes administered with or without paclitaxel in vivo and demonstrated that mesenchymal‐like tumours do not always show resistance to chemotherapy. EMT scoring is thus a promising, versatile tool for the objective and systematic investigation of EMT roles and dynamics in cancer progression, treatment response and survival.

Subfields: Cancer Research, Oncology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/806454bfa6351994541ea06d499dddfa09234f77

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Aviv Regev
2. K. Yeung
3. Jing Yang

In Oncology

1. K. Yeung
2. Jing Yang
3. R. Weinberg

Citations in the corpus

• Epithelial–mesenchymal transition in tumor metastasis (2016, background): “Additional biomarkers, such as a transcriptomic EMT signature (Tan et al., 2014) from primary tumors or circulating tumor cells.”
• Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer (2017, background): “…the p-EMT program is a stronger predictor of nodal metastasis and local invasion (Figure S7I) than either the TCGA mesenchymal program or conventional EMT signatures, both of which primarily reflect CAF frequency (Figures S4A and S7I) (Cancer Genome Atlas Network, 2015; Tan et al., 2014).”
• Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis (2015, background): “Recently, an important quantitative metric – an “EMT score” – has been proposed to represent the overall proclivity of a cell line or primary tumor toward undergoing EMT, however, it largely ignores the cellular heterogeneity and possible clonal heterogeneity inherent to a particular cell line (70).”
• Mathematical Modelling of Molecular Pathways Enabling Tumour Cell Invasion and Migration (2015, background): “[120] none of the genes of our EMT module were included.”