title: Elevated interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) is a poor prognostic marker in pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) gene from IFITs family is one gene among hundreds of IFN-stimulated genes. The potential role of IFIT3 in cancer is scarcely understood. In addition, the clinical relevance of IFIT3 is not yet known in pancreatic ductal adenocarcinoma (PDAC). We evaluated the prognostic significance of this gene in PDAC patients.
  
  
  METHODS
  The expression of IFIT3 was analyzed in pancreatic cancer cell lines with different metastatic potential (FG and L3.6pl) and one established gemcitabine resistant cell variant-L3.6plGres. Second, we analyzed the protein expression in tissue microarrays (TMA) from specimens of 254 radically resected patients with pancreatic adenocarcinoma. The prognostic relevance of IFIT3 was evaluated by the Kaplan-Meier and Cox regression analysis.
  
  
  RESULTS
  L3.6pl cells with an aggressive capacity showed a significant higher expression of IFIT3 as compared to FG cells. IFIT3 was accumulated in gemcitabine resistant cells. Overexpression of IFIT3 increased the resistance of apoptosis against gemcitabine treatment. Patients who had high expression of IFIT3 (32%) and received chemotherapy had a statistically significant reduced survival in multivariate analysis.
  
  
  CONCLUSIONS
  High expression of IFIT3 enhances anti-apoptotic activity and chemotherapy resistance of PDAC cells. High expression of IFIT3 was independently correlated to shorter patients' survival and may serve as a prognostic marker.
authors.affiliation: Department of General, Visceral und Vascular Surgery, Otto-von-Guericke University, Leipziger Straße 44, Magdeburg, 39120, Germany.|General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of General, Visceral und Vascular Surgery, Friedrich-Schiller University, Jena, Germany.
authors.forename: Annelore
authors.initials: A
authors.lastname: Altendorf-Hofmann
authors.affiliation: Department of General, Visceral und Vascular Surgery, Charite ́University Medical Center, Berlin, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Pozios
authors.affiliation: Department of General, Visceral und Vascular Surgery, Otto-von-Guericke University, Leipziger Straße 44, Magdeburg, 39120, Germany.|General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Camaj
authors.affiliation: Department of General, Visceral und Vascular Surgery, Otto-von-Guericke University, Leipziger Straße 44, Magdeburg, 39120, Germany.
authors.forename: Therese
authors.initials: T
authors.lastname: Däberitz
authors.affiliation: Department of General, Visceral und Vascular Surgery, Ludwig-Maximilian-University (LMU), Munich, Germany.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General, Visceral und Vascular Surgery, Ludwig-Maximilian-University (LMU), Munich, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Niess
authors.affiliation: Department of General, Visceral und Vascular Surgery, Charite ́University Medical Center, Berlin, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Seeliger
authors.affiliation: Department of General, Visceral und Vascular Surgery, Otto-von-Guericke University, Leipziger Straße 44, Magdeburg, 39120, Germany.|General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Popp
authors.affiliation: Department of General, Visceral und Vascular Surgery, Otto-von-Guericke University, Leipziger Straße 44, Magdeburg, 39120, Germany.|General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Betzler
authors.affiliation: Department of General, Visceral und Vascular Surgery, Friedrich-Schiller University, Jena, Germany.
authors.forename: Utz
authors.initials: U
authors.lastname: Settmacher
authors.affiliation: Department of General, Visceral und Vascular Surgery, Ludwig-Maximilian-University (LMU), Munich, Germany.
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Jauch
authors.affiliation: Department of General, Visceral und Vascular Surgery, Otto-von-Guericke University, Leipziger Straße 44, Magdeburg, 39120, Germany. christiane.bruns@med.ovgu.de.|General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany. christiane.bruns@med.ovgu.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Bruns
authors.affiliation: Institute of Pathology, Ludwig-Maximilian-University (LMU), Thalkirchnerstr. 36, Munich, 80337, Germany. Thomas.Knoesel@med.uni-muenchen.de.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0002-1822-0197
authors.initials: T
authors.lastname: Knösel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; C116468:IFIT3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Chemotherapy resistance; IFIT3; Pancreatic ductal adenocarcinoma; Tissue microarray