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PMID: 25214461 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

EMBO molecular medicine ·Vol. 6 ·No. 10 ·2014-10-00 ·Pages 1279-93

Tan TZ, Miow QH, Miki Y, Noda T, Mori S, Huang RY, Thiery JP

Abstract

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.

Keywords
drug response epithelial‐mesenchymal transition gene expression signature microarray prognosis
MeSH Terms
Antineoplastic Agents/therapeutic use Breast Neoplasms/drug therapy,genetics Cell Line, Tumor Colorectal Neoplasms/drug therapy,genetics Disease-Free Survival Epithelial-Mesenchymal Transition/drug effects,genetics Female Gene Expression Regulation, Neoplastic/drug effects Humans Lung Neoplasms/drug therapy,genetics Neoplasms/drug therapy,genetics Oligonucleotide Array Sequence Analysis Ovarian Neoplasms/drug therapy,genetics Stomach Neoplasms/drug therapy,genetics Transcriptome/drug effects,genetics Treatment Outcome Urinary Bladder Neoplasms/drug therapy,genetics
Chemicals
Antineoplastic Agents
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Tan Tuan Zea
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
Miow Qing Hao
Institute of Molecular and Cell Biology, A*STAR, Singapore.
Miki Yoshio
Cancer Institute of Japanese Foundation for Cancer Research, Kyoto, Japan.
Noda Tetsuo
Cancer Institute of Japanese Foundation for Cancer Research, Kyoto, Japan.
Mori Seiichi
Cancer Institute of Japanese Foundation for Cancer Research, Kyoto, Japan.
Huang Ruby Yun-Ju
Cancer Science Institute of Singapore, National University of Singapore, Singapore Department of Obstetrics and Gynaecology, National University Health System, Singapore.
Thiery Jean Paul
Cancer 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@imcb.a-star.edu.sg.
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Article Info
Journal
EMBO molecular medicine
Abbr.
EMBO Mol Med
ISSN
1757-4684
DOI
10.15252/emmm.201404208
Email
jpthiery@imcb.a-star.edu.sg
Published
2014-10-00
Pages
1279-93
Language
English
Region
England
NLM ID
101487380
PMCID
PMC4287932
Subset
IM
External Links
PubMed source DOI: 10.15252/emmm.201404208 PMC Full Text View journal details
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