title: KRAS mutation status is associated with specific pattern of genes expression in pancreatic adenocarcinoma.
abstract: OBJECTIVE
  To evaluate potential differences at a molecular level between KRAS mutant tumors (MT) and KRAS wild-type (WT) pancreatic tumors and the biological and prognostic significance of different KRAS mutations.
  
  
  METHODS
  Expression of a panel of 29 genes was analyzed in KRAS WT and MT tumors. Effects of KRAS mutation and gene expression levels were assessed on patients' survival.
  
  
  RESULTS
  MUC6 (p = 0.009), HGF (p = 0.011), VEGFR-2 (p = 0.020) and VEGFB (p = 0.026) were significantly more expressed and SMAD4 was less suppressed (p = 0.003) in WT KRAS. Contrariwise, SHH (p = 0.012) and IHH (p = 0.031) were more expressed in MT KRAS patients. No OS difference was found between WT and MT KRAS tumors.
  
  
  CONCLUSIONS
  KRAS mutation status seems to identify two different subtypes of pancreatic ductal adenocarcinoma with similar outcome but distinct molecular features and probably different therapeutic targets.
authors.affiliation: Department of Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle Marche, via Conca 71, 60126 Ancona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bittoni
authors.affiliation: Department of Specialistic Clinical & Odontostomatological Sciences, Polytechnic University of Marche, Ancona 60131, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Piva
authors.affiliation: Department of Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle Marche, via Conca 71, 60126 Ancona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.affiliation: Department of Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle Marche, via Conca 71, 60126 Ancona, Italy.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Andrikou
authors.affiliation: Department of Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle Marche, via Conca 71, 60126 Ancona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Conti
authors.affiliation: Department of Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle Marche, via Conca 71, 60126 Ancona, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Loretelli
authors.affiliation: Department of Pathology, AOU Ospedali Riuniti, Università Politecnica delle Marche, via Conca 71, 60126 Ancona, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mandolesi
authors.affiliation: Department of Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle Marche, via Conca 71, 60126 Ancona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lanese
authors.affiliation: Department of Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle Marche, via Conca 71, 60126 Ancona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pellei
authors.affiliation: Department of Pathology, AOU Ospedali Riuniti, Università Politecnica delle Marche, via Conca 71, 60126 Ancona, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Scarpelli
authors.affiliation: Department of Specialistic Clinical & Odontostomatological Sciences, Polytechnic University of Marche, Ancona 60131, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Principato
authors.affiliation: Department of Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle Marche, via Conca 71, 60126 Ancona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D009363:Neoplasm Proteins; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; nucleotide variations; overall survival; pancreatic ductal adenocarcinoma; splicing