title: Cross-species antibody microarray interrogation identifies a 3-protein panel of plasma biomarkers for early diagnosis of pancreas cancer.
abstract: OBJECTIVE
  Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related death in the United States, and its incidence is on the rise. Advanced disease is nearly uniformly lethal, emphasizing the need to identify PDA at its earliest stages. To discover early biomarkers of PDA, we evaluated the circulating proteome in murine preinvasive and invasive plasma samples and human prediagnostic and diagnostic samples.
  
  
  METHODS
  Using a customized antibody microarray platform containing >4,000 features, we interrogated plasma samples spanning preinvasive and invasive disease from a highly faithful mouse model of PDA. In parallel, we mined prediagnostic plasma from women in the Women's Health Initiative (WHI) who would later succumb to PDA together with matched, cancer-free control samples. Samples collected after an establishing diagnosis of PDA were also interrogated to further validate markers.
  
  
  RESULTS
  We identified ERBB2 and TNC in our cross-species analyses, and multiple antibodies identified ESR1 in prediagnostic plasma from people that succumb to PDA. This 3-marker panel had an AUC of 0.86 (95% confidence interval [CI], 0.76-0.96) for the diagnostic cohort that increased to 0.97 (95% CI, 0.92-1.0) with CA19-9 included. The 3-marker panel also had an AUC of 0.68 (95% CI, 0.58-0.77) for the prediagnostic cohort.
  
  
  CONCLUSIONS
  We identified potential disease detection markers in plasma up to 4 years before death from PDA with superior performance to CA19-9. These markers might be especially useful in high-risk cohorts to diagnose early, resectable disease, particularly in patients that do not produce CA19-9.
authors.affiliation: Translational Research Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Justin E
authors.initials: JE
authors.lastname: Mirus
authors.affiliation: Translational Research Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Yuzheng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Translational Research Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Li
authors.affiliation: University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Lokshin
authors.affiliation: Translational Research Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Ross L
authors.initials: RL
authors.lastname: Prentice
authors.affiliation: Translational Research Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Division of Medical Oncology, University of Washington School of Medicine, Seattle, Washington. srh@fhcrc.org plampe@fhcrc.org.
authors.forename: Sunil R
authors.initials: SR
authors.lastname: Hingorani
authors.affiliation: Translational Research Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. srh@fhcrc.org plampe@fhcrc.org.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Lampe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor