title: Development and Clinical Validation of a Blood Test Based on 29-Gene Expression for Early Detection of Colorectal Cancer.
abstract: OBJECTIVE
  A blood test for early detection of colorectal cancer is a valuable tool for testing asymptomatic individuals and reducing colorectal cancer-related mortality. The objective of this study was to develop and validate a novel blood test able to differentiate patients with colorectal cancer and adenomatous polyps (AP) from individuals with a negative colonoscopy.
  
  
  METHODS
  A case-control, multicenter clinical study was designed to collect blood samples from patients referred for colonoscopy or surgery. Predictive algorithms were developed on 75 controls, 61 large AP (LAP) ≥1 cm, and 45 colorectal cancer cases and independently validated on 74 controls, 42 LAP, and 52 colorectal cancer cases (23 stages I-II) as well as on 245 cases including other colorectal findings and diseases other than colorectal cancer. The test is based on a 29-gene panel expressed in peripheral blood mononuclear cells alone or in combination with established plasma tumor markers.
  
  
  RESULTS
  The 29-gene algorithm detected colorectal cancer and LAP with a sensitivity of 79.5% and 55.4%, respectively, with 90.0% specificity. Combination with the protein tumor markers carcinoembryonic antigen (CEA) and CYFRA21-2 resulted in a specificity increase (92.2%) with a sensitivity for colorectal cancer and LAP detection of 78.1% and 52.3%, respectively.
  
  
  CONCLUSIONS
  We report the validation of a novel blood test, Colox®, for the detection of colorectal cancer and LAP based on a 29-gene panel and the CEA and CYFRA21-1 plasma biomarkers. The performance and convenience of this routine blood test provide physicians a useful tool to test average-risk individuals unwilling to undergo upfront colonoscopy. Clin Cancer Res; 22(18); 4604-11. ©2016 AACR.
authors.affiliation: Novigenix SA, Epalinges, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Ciarloni
authors.affiliation: Novigenix SA, Epalinges, Switzerland.
authors.forename: Sahar Hosseinian
authors.initials: SH
authors.lastname: Ehrensberger
authors.affiliation: Novigenix SA, Epalinges, Switzerland.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Imaizumi
authors.affiliation: Novigenix SA, Epalinges, Switzerland.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Monnier-Benoit
authors.affiliation: Department of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Nichita
authors.affiliation: Asan Medical Centre, Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Myung
authors.affiliation: Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Joo Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Severance Hospital, Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Si Young
authors.initials: SY
authors.lastname: Song
authors.affiliation: Severance Hospital, Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Tae Il
authors.initials: TI
authors.lastname: Kim
authors.affiliation: Spital Thun, Gastroenterology, Thun, Switzerland.
authors.forename: Boudewijn
authors.initials: B
authors.lastname: van der Weg
authors.affiliation: Kantonsspital Liestal, Gastroenterology, Hepatology and Nutrition Department, University Hospital, Liestal, Switzerland.
authors.forename: Rémy
authors.initials: R
authors.lastname: Meier
authors.affiliation: Kantonsspital St. Gallen, Department of Gastroenterology and Hepatology, St. Gallen, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Borovicka
authors.affiliation: Universitätsspital Basel, Department of Biomedicine, Basel, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Beglinger
authors.affiliation: Ensemble Hospitalier de la Côte, Surgery Services, Morges, Switzerland.
authors.forename: Cédric
authors.initials: C
authors.lastname: Vallet
authors.affiliation: Clinique Cecil, Gastroenterology, Lausanne, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Maerten
authors.affiliation: Novigenix SA, Epalinges, Switzerland. Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland. curzio.ruegg@unifr.ch gian.dorta@chuv.ch.
authors.forename: Curzio
authors.initials: C
authors.lastname: Rüegg
authors.affiliation: Department of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. curzio.ruegg@unifr.ch gian.dorta@chuv.ch.
authors.forename: Gian
authors.initials: G
authors.lastname: Dorta
mesh_terms: D018256:Adenomatous Polyps / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D000368:Aged; D000465:Algorithms; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics*; D055088:Early Detection of Cancer / Q000379:methods / Q000592:standards; D005260:Female; D006801:Humans; D000073890:Liquid Biopsy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm