title: Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients.
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.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Tuan Zea
authors.initials: TZ
authors.lastname: Tan
authors.affiliation: Institute of Molecular and Cell Biology, A*STAR, Singapore.
authors.forename: Qing Hao
authors.initials: QH
authors.lastname: Miow
authors.affiliation: Cancer Institute of Japanese Foundation for Cancer Research, Kyoto, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Cancer Institute of Japanese Foundation for Cancer Research, Kyoto, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Noda
authors.affiliation: Cancer Institute of Japanese Foundation for Cancer Research, Kyoto, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Mori
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore Department of Obstetrics and Gynaecology, National University Health System, Singapore.
authors.forename: Ruby Yun-Ju
authors.initials: RY
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Thiery
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics; D059467:Transcriptome / Q000187:drug effects* / Q000235:genetics; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents
keywords: drug response; epithelial‐mesenchymal transition; gene expression signature; microarray; prognosis