title: Empirical evaluation demonstrated importance of validating biomarkers for early detection of cancer in screening settings to limit the number of false-positive findings.
abstract: Search for biomarkers for early detection of cancer is a very active area of research, but most studies are done in clinical rather than screening settings. We aimed to empirically evaluate the role of study setting for early detection marker identification and validation.
  
  
  
  A panel of 92 candidate cancer protein markers was measured in 35 clinically identified colorectal cancer patients and 35 colorectal cancer patients identified at screening colonoscopy. For each case group, we selected 38 controls without colorectal neoplasms at screening colonoscopy. Single-, two- and three-marker combinations discriminating cases and controls were identified in each setting and subsequently validated in the alternative setting.
  
  
  
  In all scenarios, a higher number of predictive biomarkers were initially detected in the clinical setting, but a substantially lower proportion of identified biomarkers could subsequently be confirmed in the screening setting. Confirmation rates were 50.0%, 84.5%, and 74.2% for one-, two-, and three-marker algorithms identified in the screening setting and were 42.9%, 18.6%, and 25.7% for algorithms identified in the clinical setting.
  
  
  
  Validation of early detection markers of cancer in a true screening setting is important to limit the number of false-positive findings.
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Baden-Württemberg, Germany.
authors.forename: Hongda
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Baden-Württemberg, Germany.
authors.forename: Phillip
authors.initials: P
authors.lastname: Knebel
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Baden-Württemberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120 Heidelberg, Baden-Württemberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Baden-Württemberg, Germany. Electronic address: h.brenner@dkfz-heidelberg.de.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis*; D055088:Early Detection of Cancer / Q000379:methods*; D005189:False Positive Reactions; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarker identification; Early detection; Methodology; Research design; Study setting; Validity