title: Desmogleins as prognostic biomarkers in resected pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  Frequent disease relapse and a lack of effective therapies result in a very poor outcome in pancreatic ductal adenocarcinoma (PDAC) patients. Thus, identification of prognostic biomarkers and possible therapeutic targets is essential. Besides their function in cell-cell adhesion, desmogleins may play a role in tumour progression and invasion that has not been investigated in PDAC to date. This study evaluated desmoglein expression as a biomarker in PDAC.
  
  
  METHODS
  Using immunohistochemistry, we examined desmoglein 1 (DSG1), desmoglein 2 (DSG2) and desmoglein 3 (DSG3) expression in the tumour tissue of 165 resected PDAC cases. Expression levels were correlated to the patients' clinicopathological parameters and postoperative survival times. We confirmed these results in two independent gene expression data sets.
  
  
  RESULTS
  A total of 36% of the tumours showed high DSG3 expression that correlated significantly with shorter patient survival (P=0.011) and poor tumour differentiation (P<0.001), whereas no such association was detected for DSG1 or DSG2. In RNA-Seq data and in microarray expression data, high DSG3 expression correlated significantly with poor survival (P=0.000356 and P=0.00499).
  
  
  CONCLUSIONS
  We identify DSG3 as a negative prognostic biomarker in resected PDAC, as high DSG3 expression is associated with poor overall survival and poor tumour-specific survival. These findings suggest DSG3 and its downstream signalling pathways as possible therapeutic targets in DSG3-expressing PDAC.
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University, Thalkirchner Strasse 36, Munich 80337, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Ormanns
authors.affiliation: Department of General, Visceral and Vascular Surgery, Jena University Hospital, Erlanger Allee 101, Jena 07747, Germany.
authors.forename: Annelore
authors.initials: A
authors.lastname: Altendorf-Hofmann
authors.affiliation: Cancer Research UK, Beatson Institute, Glasgow G61 1BD, UK.
authors.forename: Rene
authors.initials: R
authors.lastname: Jackstadt
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University, Thalkirchner Strasse 36, Munich 80337, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Horst
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University, Thalkirchner Strasse 36, Munich 80337, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Assmann
authors.affiliation: Department of Surgery, University Hospital Magdeburg, Leipziger Strasse 44, Magdeburg 39120, Germany.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Surgery, University Hospital Magdeburg, Leipziger Strasse 44, Magdeburg 39120, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Bruns
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University, Thalkirchner Strasse 36, Munich 80337, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University, Thalkirchner Strasse 36, Munich 80337, Germany.
authors.forename: Thomas
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 / Q000235:genetics / Q000378:metabolism / Q000601:surgery*; D051183:Desmoglein 1 / Q000235:genetics* / Q000378:metabolism*; D051301:Desmoglein 2 / Q000235:genetics / Q000378:metabolism; D051184:Desmoglein 3 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000601:surgery*; D011379:Prognosis; D017423:Sequence Analysis, RNA; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C495297:DSG1 protein, human; C495314:DSG2 protein, human; C071894:DSG3 protein, human; D051183:Desmoglein 1; D051301:Desmoglein 2; D051184:Desmoglein 3