title: A combination of serum markers for the early detection of colorectal cancer.
abstract: OBJECTIVE
  Fecal occult blood testing is recommended as first-line screening to detect colorectal cancer (CRC). We evaluated markers and marker combinations in serum as an alternative to improve the detection of CRC.
  
  
  METHODS
  Using penalized logistic regression, 6 markers were selected for evaluation in 1,027 samples (301 CRC patients, 143 patients with adenoma, 266 controls, 141 disease controls, and 176 patients with other cancer). The diagnostic performance of each marker and of marker combinations was assessed.
  
  
  RESULTS
  To detect CRC from serum samples, we tested 22 biomarkers. Six markers were selected for a marker combination, including the known tumor markers CEA (carcinoembryonic antigen) and CYFRA 21-1 as well as novel markers or markers that are less routinely used for the detection of CRC: ferritin, osteopontin (OPN), anti-p53, and seprase. CEA showed the best sensitivity at 95% specificity with 43.9%, followed by seprase (42.4%), CYFRA 21-1 (35.5%), OPN (30.2%), ferritin (23.9%), and anti-p53 (20.0%). A combination of these markers gave 69.6% sensitivity at 95% specificity and 58.7% at 98% specificity. Focusing on International Union against Cancer (UICC) stages 0-III reduced the sensitivity slightly to 68.0% and 53.3%, respectively. In a subcollective, with matched stool samples (75 CRC cases and 234 controls), the sensitivity of the marker combination was comparable with fecal immunochemical testing (FIT) with 82.4% and 68.9% versus 81.8% and 72.7% at 95% and 98% specificity, respectively.
  
  
  CONCLUSIONS
  The performance of the serum marker combination is comparable with FIT. This provides a novel tool for CRC screening to trigger a follow-up colonoscopy for a final diagnosis.
authors.affiliation: Department of New Technologies, Roche Diagnostics GmbH, Penzberg, Germany. norbert.wild@roche.com
authors.forename: Norbert
authors.initials: N
authors.lastname: Wild
authors.forename: Herbert
authors.initials: H
authors.lastname: Andres
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rollinger
authors.forename: Friedemann
authors.initials: F
authors.lastname: Krause
authors.forename: Peter
authors.initials: P
authors.lastname: Dilba
authors.forename: Michael
authors.initials: M
authors.lastname: Tacke
authors.forename: Johann
authors.initials: J
authors.lastname: Karl
mesh_terms: D000236:Adenoma / Q000097:blood / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009780:Occult Blood; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor