title: A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest.
abstract: BACKGROUND
  Currently, prognostication for pancreatic ductal adenocarcinoma (PDAC) is based upon a coarse clinical staging system. Thus, more accurate prognostic tests are needed for PDAC patients to aid treatment decisions.
  
  
  RESULTS
  Affymetrix gene expression profiling was carried out on 15 human PDAC tumors and from the data we identified a 13-gene expression signature (risk score) that correlated with patient survival. The gene expression risk score was then independently validated using published gene expression data and survival data for an additional 101 patients with pancreatic cancer. Patients with high-risk scores had significantly higher risk of death compared to patients with low-risk scores (HR 2.27, p = 0.002). When the 13-gene score was combined with lymph node status the risk-score further discriminated the length of patient survival time (p<0.001). Patients with a high-risk score had poor survival independent of nodal status; however, nodal status increased predictability for survival in patients with a low-risk gene signature score (low-risk N1 vs. low-risk N0: HR = 2.0, p = 0.002). While AJCC stage correlated with patient survival (p = 0.03), the 13-gene score was superior at predicting survival. Of the 13 genes comprising the predictive model, four have been shown to be important in PDAC, six are unreported in PDAC but important in other cancers, and three are unreported in any cancer.
  
  
  CONCLUSIONS
  We identified a 13-gene expression signature that predicts survival of PDAC patients and could prove useful for making treatment decisions. This risk score should be evaluated prospectively in clinical trials for prognostication and for predicting response to chemotherapy. Investigation of new genes identified in our model may lead to novel therapeutic targets.
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Newhook
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Edik M
authors.initials: EM
authors.lastname: Blais
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: James M
authors.initials: JM
authors.lastname: Lindberg
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Adair
authors.affiliation: Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xin
authors.affiliation: Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Jae K
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Papin
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Parsons
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Bauer
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011379:Prognosis; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis; D015854:Up-Regulation / Q000235:genetics