Research

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

Tan TZ1, Miow QH2, Miki Y3, Noda T3, Mori S3, Huang RY4, Thiery JP5

1Cancer Science Institute of Singapore, National University of Singapore, Singapore.
2Institute of Molecular and Cell Biology, A*STAR, Singapore.
3Cancer Institute of Japanese Foundation for Cancer Research, Kyoto, Japan.
4Cancer Science Institute of Singapore, National University of Singapore, Singapore Department of Obstetrics and Gynaecology, National University Health System, Singapore.
5Cancer Science Institute of Singapore, National University of Singapore, Singapore Institute of Molecular and Cell Biology, A*STAR, Singapore Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore jpthiery[at]imcb.a-star.edu.sg.

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.

jpt2014

Pubmed