title: A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease. For patients with localized PDAC, surgery is the best option, but with a median survival of less than 2 years and a difficult and prolonged postoperative course for most, there is an urgent need to better identify patients who have the most aggressive disease.
  
  
  RESULTS
  We analyzed the gene expression profiles of primary tumors from patients with localized compared to metastatic disease and identified a six-gene signature associated with metastatic disease. We evaluated the prognostic potential of this signature in a training set of 34 patients with localized and resected PDAC and selected a cut-point associated with outcome using X-tile. We then applied this cut-point to an independent test set of 67 patients with localized and resected PDAC and found that our signature was independently predictive of survival and superior to established clinical prognostic factors such as grade, tumor size, and nodal status, with a hazard ratio of 4.1 (95% confidence interval [CI] 1.7-10.0). Patients defined to be high-risk patients by the six-gene signature had a 1-year survival rate of 55% compared to 91% in the low-risk group.
  
  
  CONCLUSIONS
  Our six-gene signature may be used to better stage PDAC patients and assist in the difficult treatment decisions of surgery and to select patients whose tumor biology may benefit most from neoadjuvant therapy. The use of this six-gene signature should be investigated in prospective patient cohorts, and if confirmed, in future PDAC clinical trials, its potential as a biomarker should be investigated. Genes in this signature, or the pathways that they fall into, may represent new therapeutic targets. Please see later in the article for the Editors' Summary.
authors.affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Jeran K
authors.initials: JK
authors.lastname: Stratford
authors.forename: David J
authors.initials: DJ
authors.lastname: Bentrem
authors.forename: Judy M
authors.initials: JM
authors.lastname: Anderson
authors.forename: Cheng
authors.initials: C
authors.lastname: Fan
authors.forename: Keith A
authors.initials: KA
authors.lastname: Volmar
authors.forename: J S
authors.initials: JS
authors.lastname: Marron
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Routh
authors.forename: Laura S
authors.initials: LS
authors.lastname: Caskey
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Samuel
authors.forename: Channing J
authors.initials: CJ
authors.lastname: Der
authors.forename: Leigh B
authors.initials: LB
authors.lastname: Thorne
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Calvo
authors.forename: Hong Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Mark S
authors.initials: MS
authors.lastname: Talamonti
authors.forename: Christine A
authors.initials: CA
authors.lastname: Iacobuzio-Donahue
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hollingsworth
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Jen Jen
authors.initials: JJ
authors.lastname: Yeh
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis