title: Relevance of MicroRNA200 Family and MicroRNA205 for Epithelial to Mesenchymal Transition and Clinical Outcome in Biliary Tract Cancer Patients.
abstract: Extensive stromal interaction is one reason for the dismal outcome of biliary tract cancer (BTC) patients. Epithelial to mesenchymal transition (EMT) is involved in tumor invasion and metastasis and is partly regulated by microRNAs (miRs). This study explores the expression of anti-EMT miR200 family (miR141, -200a/b/c, -429) and miR205 as well as the EMT-related proteinsE-cadherin and vimentin in a panel of BTC cell lines and clinical specimens by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry, respectively. MicroRNA expression was correlated to (i) the expression patterns ofE-cadherin and vimentin; (ii) clinicopathological characteristics; and (iii) survival data. MicroRNA-200 family and miR205 were expressed in all BTC cells and clinical specimens.E-cadherin and vimentin showed a mutually exclusive expression pattern in both, in vitro and in vivo. Expression of miR200 family members positively correlated withE-cadherin and negatively with vimentin expression in BTC cells and specimens. High expression of miR200 family members (but not miR205) andE-cadherin was associated with longer survival, while low miR200 family and high vimentin expression was a predictor of unfavorable survival. Overall, the current study demonstrates the relevance of the miR200 family in EMT of BTC tumors and suggests these miRs as predictors for positive outcome.
authors.affiliation: Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg 5020, Austria. r.urbas@salk.at.
authors.forename: Romana
authors.initials: R
authors.lastname: Urbas
authors.affiliation: Laboratory for Tumour Biology and Experimental Therapies (TREAT), Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg 5020, Austria. christian.mayr@pmu.ac.at.|Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg 5020, Austria. christian.mayr@pmu.ac.at.
authors.forename: Christian
authors.initials: C
authors.lastname: Mayr
authors.affiliation: Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg 5020, Austria. e.klieser@salk.at.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Klieser
authors.affiliation: Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg 5020, Austria. j.fuereder@gmx.net.
authors.forename: Julia
authors.initials: J
authors.lastname: Fuereder
authors.affiliation: Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg 5020, Austria. doris.bach@gmx.at.
authors.forename: Doris
authors.initials: D
authors.lastname: Bach
authors.affiliation: Department of Visceral-, Transplant- and Thoracic Surgery, Medical University of Innsbruck, Innsbruck 6020, Austria. stefan.staettner@tirol-kliniken.at.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stättner
authors.affiliation: Department of Visceral-, Transplant- and Thoracic Surgery, Medical University of Innsbruck, Innsbruck 6020, Austria. florian.primavesi@tirol-kliniken.at.
authors.forename: Florian
authors.initials: F
authors.lastname: Primavesi
authors.affiliation: Department of Surgery, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg 5020, Austria. ta.jaeger@salk.at.
authors.forename: Tarkan
authors.initials: T
authors.lastname: Jaeger
authors.affiliation: Research Unit for Non-Coding RNA and Genome Editing in Cancer, Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz 8036, Austria. Stefanie.Stanzer@klinikum-graz.at.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Stanzer
authors.affiliation: Research Unit for Non-Coding RNA and Genome Editing in Cancer, Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz 8036, Austria. anna.lena.ress@gmail.com.
authors.forename: Anna Lena
authors.initials: AL
authors.lastname: Ress
authors.affiliation: Laboratory for Tumour Biology and Experimental Therapies (TREAT), Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg 5020, Austria. mloeffelberger.bma-b2012@fh-salzburg.ac.at.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Löffelberger
authors.affiliation: Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg 5020, Austria. and.wagner@salk.at.
authors.forename: Andrej
authors.initials: A
authors.lastname: Wagner
authors.affiliation: Laboratory for Tumour Biology and Experimental Therapies (TREAT), Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg 5020, Austria. frieder.berr@pmu.ac.at.|Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg 5020, Austria. frieder.berr@pmu.ac.at.
authors.forename: Frieder
authors.initials: F
authors.lastname: Berr
authors.affiliation: Laboratory for Tumour Biology and Experimental Therapies (TREAT), Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg 5020, Austria. markus.ritter@pmu.ac.at.|Department for Radon Therapy Research, Ludwig Boltzmann Cluster for Arthritis and Rehabilitation, Salzburg 5020, Austria. markus.ritter@pmu.ac.at.
authors.forename: Markus
authors.initials: M
authors.lastname: Ritter
authors.affiliation: Research Unit for Non-Coding RNA and Genome Editing in Cancer, Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz 8036, Austria. martin.pichler@medunigraz.at.
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
authors.affiliation: Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg 5020, Austria. d.neureiter@salk.at.
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.affiliation: Laboratory for Tumour Biology and Experimental Therapies (TREAT), Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg 5020, Austria. t.kiesslich@salk.at.|Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg 5020, Austria. t.kiesslich@salk.at.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kiesslich
mesh_terms: D001661:Biliary Tract Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics* / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: biliary tract cancer; epithelial to mesenchymal transition; microRNA-200 family; microRNA-205