title: A novel embryonic plasticity gene signature that predicts metastatic competence and clinical outcome.
abstract: Currently, very few prognosticators accurately predict metastasis in cancer patients. In order to complete the metastatic cascade and successfully colonize distant sites, carcinoma cells undergo dynamic epithelial-mesenchymal-transition (EMT) and its reversal, mesenchymal-epithelial-transition (MET). While EMT-centric signatures correlate with response to therapy, they are unable to predict metastatic outcome. One reason is due to the wide range of transient phenotypes required for a tumor cell to disseminate and recreate a similar histology at distant sites. Since such dynamic cellular processes are also seen during embryo development (epithelial-like epiblast cells undergo transient EMT to generate the mesoderm, which eventually redifferentiates into epithelial tissues by MET), we sought to utilize this unique and highly conserved property of cellular plasticity to predict metastasis. Here we present the identification of a novel prognostic gene expression signature derived from mouse embryonic day 6.5 that is representative of extensive cellular plasticity, and predicts metastatic competence in human breast tumor cells. This signature may thus complement conventional clinical parameters to offer accurate prediction for outcome among multiple classes of breast cancer patients.
authors.affiliation: Department of Translational Molecular Pathology.
authors.forename: Rama
authors.initials: R
authors.lastname: Soundararajan
authors.affiliation: Department of Translational Molecular Pathology.
authors.forename: Anurag N
authors.initials: AN
authors.lastname: Paranjape
authors.affiliation: Department of Translational Molecular Pathology.
authors.forename: Valentin
authors.initials: V
authors.lastname: Barsan
authors.affiliation: Department of Integrative Biology and Pharmacology, School of Medicine; School of Biomedical Informatics; The University of Texas Health Sciences Center at Houston, Houston, Texas.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Chang
authors.affiliation: 1] Department of Translational Molecular Pathology [2] Metastasis Research Center [3] Center for Stem Cells and Developmental Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sendurai A
authors.initials: SA
authors.lastname: Mani
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000502:physiology; D009362:Neoplasm Metastasis; D059467:Transcriptome; D016896:Treatment Outcome