title: Identification of potential prognostic biomarkers in patients with untreated, advanced pancreatic cancer from a phase 3 trial (Cancer and Leukemia Group B 80303).
abstract: BACKGROUND
  Patients with advanced stage adenocarcinoma of the pancreas have a poor prognosis. The identification of prognostic and/or predictive biomarkers may help stratify patients so that therapy can be individualized.
  
  
  METHODS
  Serum samples from patients enrolled in the Cancer and Leukemia Group B 80303 phase 3 trial, "Randomized Study of Gemcitabine With Versus Without Bevacizumab in Patients With Locally Advanced or Metastatic Adenocarcinoma of the Pancreas" were used to discover novel biomarkers. For the discovery phase, 40 sera were selected based on length of survival and type of therapy, and subjected to liquid chromatography coupled to tandem mass spectrometry analysis (LC-MS-MS). The top features (proteins) were then further selected for validation by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Quantification by nano-LC-MS-MS resulted in 1452 peptides mapping to 156 proteins across all 40 samples, 92 of which had 2 or more peptides. After curation of the data, the authors selected 1 putative prognostic protein, alpha 1-antichymotrypsin (AACT), and 2 putative predictive proteins, histidine-rich glycoprotein (HRG) and complement factor H (CFH), for validation by ELISA. AACT was found to be negatively correlated with overall survival (τ = -0.30 [-0.38, -0.22]; P < .00001). There was no evidence for interaction with bevacizumab and HRG, but there was some evidence for a weak positive correlation of HRG with overall survival (τ = 0.11 [0.03, 0.19]; P < .01). CFH was found to be neither a predictive nor a prognostic factor for overall survival.
  
  
  CONCLUSIONS
  AACT may be a useful prognostic marker in patients with advanced stage pancreatic carcinoma, although additional validation studies are needed.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Roberts
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Campa
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Gottlin
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
authors.forename: Kouros
authors.initials: K
authors.lastname: Owzar
authors.forename: Hedy L
authors.initials: HL
authors.lastname: Kindler
authors.forename: Alan P
authors.initials: AP
authors.lastname: Venook
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
authors.forename: Eileen M
authors.initials: EM
authors.lastname: O'Reilly
authors.forename: Edward F
authors.initials: EF
authors.lastname: Patz
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis*; D011379:Prognosis; D000514:alpha 1-Antichymotrypsin / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D000514:alpha 1-Antichymotrypsin