title: A novel multiplex-protein array for serum diagnostics of colon cancer: a case-control study.
abstract: BACKGROUND
  More than 1.2 million new cases of colorectal cancer are reported each year worldwide. Despite actual screening programs, about 50% of the patients are diagnosed at advanced tumor stages presenting poor prognosis. Innovative screening tools could aid the detection at early stages and allow curative treatment interventions.
  
  
  METHODS
  A nine target multiplex serum protein biochip was generated and evaluated using a training- and validation-set of 317 highly standardized, liquid nitrogen preserved serum samples comprising controls, adenomas, and colon cancers.
  
  
  RESULTS
  Serum levels of CEA, IL-8, VEGF, S100A11, MCSF, C3adesArg, CD26, and CRP showed significant differences between cases and controls. The largest areas under the receiver operating characteristics curve were observed for CEA, IL-8, and CRP. At threshold levels yielding 90% specificity, sensitivities for CEA, IL-8 and CRP were 26%, 22%, and 17%, respectively. The most promising marker combinations were CEA + IL-8 reaching 37% sensitivity at 83% specificity and CEA + CRP with 35% sensitivity at 81% specificity. In an independent validation set CEA + IL-8 reached 47% sensitivity at 86% specificity while CEA + CRP obtained 39% sensitivity at 86% specificity. Early carcinomas were detected with 33% sensitivity for CEA + IL-8 and 28% for CEA + CRP.
  
  
  CONCLUSIONS
  Apart from CEA, IL-8, and CRP, the screening value of additional blood markers and the potential advantage of combining serum biochip testing with fecal occult blood testing needs to be studied. Multiplex biochip array technology utilizing serum samples offers an innovative approach to colorectal cancer screening.
authors.affiliation: Laboratory for Surgical Research, Department of Surgery, University of Lübeck, Ratzeburger Allee 160, D-23538, Lübeck, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Bünger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Haug
authors.forename: Maria
authors.initials: M
authors.lastname: Kelly
authors.forename: Nicole
authors.initials: N
authors.lastname: Posorski
authors.forename: Katja
authors.initials: K
authors.lastname: Klempt-Giessing
authors.forename: Andrew
authors.initials: A
authors.lastname: Cartwright
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Fitzgerald
authors.forename: Vicki
authors.initials: V
authors.lastname: Toner
authors.forename: Damien
authors.initials: D
authors.lastname: McAleer
authors.forename: Timo
authors.initials: T
authors.lastname: Gemoll
authors.forename: Tilman
authors.initials: T
authors.lastname: Laubert
authors.forename: Jürgen
authors.initials: J
authors.lastname: Büning
authors.forename: Klaus
authors.initials: K
authors.lastname: Fellermann
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Bruch
authors.forename: Uwe J
authors.initials: UJ
authors.lastname: Roblick
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.forename: Ferdinand
authors.initials: F
authors.lastname: von Eggeling
authors.forename: Jens K
authors.initials: JK
authors.lastname: Habermann
mesh_terms: D000236:Adenoma / Q000097:blood / Q000175:diagnosis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000097:blood; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000097:blood* / Q000175:diagnosis; D019295:Computational Biology; D005260:Female; D057166:High-Throughput Screening Assays; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D040081:Protein Array Analysis / Q000379:methods; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D016209:Interleukin-8; D002097:C-Reactive Protein