Z Gastroenterol 2010; 48 - P184
DOI: 10.1055/s-0030-1263628

Detector-C: A Blood-based IVD with High Sensitivity and Specificity for Early Detection and Screening of Colorectal Cancer

A Rosenthal 1, H Köppen 2, R Musikowski 3, R Schwanitz 3, J Behrendt 4, U Göbel 5, S Menzel 6, W Pommerien 7, H Grümmer 8, D Nürnberg 9, H Wichmann 10, M Pross 11, J Pertschy 12, P Nartschik 13, T Manger 14, B Unger 15, R Mantke 16, T Steinmüller 17, K Ridwelski 18, T Buthut 19, U Fleck 20, K Gellert 21, U Hildebrandt 22, R Koll 23, M Knoop 24, C Laun 25, H Lippert 26, HP Adams 1
  • 1Signature Diagnostics AG, Potsdam, Germany
  • 2Internistische Facharztpraxis, Neuruppin, Germany
  • 3Chirurgische Gemeinschaftspraxis Dres. Flöter, Musikowski & Schwanitz, Cottbus, Germany
  • 4Praxis für Innere Medizin/Gastroenterologie, Brandenburg, Germany
  • 5Facharzt für Innere Medizin, Cottbus, Germany
  • 6Praxis für Innere Medizin/Gastroenterologie/Proktologie, Potsdam, Germany
  • 7Städtisches Klinikum Brandenburg GmbH, Innere Medizin II, Brandenburg, Germany
  • 8Facharzt für Innere Medizin, Potsdam, Germany
  • 9Ruppiner Kliniken GmbH, Innere Medizin B, Neuruppin, Germany
  • 10Fachärztin für Inn. Med. u. Gastroenterologie, Potsdam, Germany
  • 11DRK-Kliniken Berlin-Köpenick, Chirurgische Klinik, Berlin, Germany
  • 12St. Johann Nepomuk Erfurt, Erfurt, Germany
  • 13Klinikum D. C. Erxleben Quedlinburg gGmbH, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Phlebologie, Proktologie, Quedlinburg, Germany
  • 14SRH Wald-Klinikum Gera gGmbH, Klinik für Allgemeine-, Viszerale und Kinderchirurgie, Gera, Germany
  • 15Klinikum Ernst von Bergmann gGmbH, Chirurgische Klinik – Allgemein- und Viszeralchirurgie, Potsdam, Germany
  • 16Städtisches Klinikum Brandenburg GmbH, Klinik für Allgemein- und Viszeralchirurgie, Brandenburg, Germany
  • 17DRK Kliniken Berlin Westend, Chirurgische Klinik, Berlin, Germany
  • 18Städtisches Klinikum Magdeburg, Klinik für Allgemein- und Viszeralchirurgie, Magdeburg, Germany
  • 19Ruppiner Kliniken GmbH, Klinik für Allgemein- und Viszeralchirurgie, Neuruppin, Germany
  • 20DRK-Krankenhaus Luckenwalde, Abteilung für Allgemein- und Viszeralchirurgie, Luckenwalde, Germany
  • 21Sana Klinikum Lichtenberg, Klinik für Allgemein- und Visceralchirurgie, Berlin, Germany
  • 22KMG Kliniken AG, Klinikum Pritzwalk, Klinik für Allgemein-, Visceral- und Gefäßchirurgie, Pritzwalk, Germany
  • 23Klinikum Uckermark GmbH, Klinik für Allgemein- und Viszeralchirurgie, Schwedt, Germany
  • 24Klinikum Frankfurt (Oder) GmbH, Abteilung für Allgemein- und Viszeralchirurgie, Frankfurt (Oder), Germany
  • 25St. Josephs Krankenhaus, Klinik für Allgemein- und Visceralchirurgie, Potsdam, Germany
  • 26Universitätsklinikum Magdeburg A.ö R., Universitätsklinik für Allgemein-, Viszeral- und Gefäßchirurgie, Magdeburg, Germany

Introduction and Aims: Colonoscopy is the gold standard for screening of colorectal cancer (CRC). However, only 5% of the screening population aged 55–75 years use colonoscopy per annum due to its inconvenience and invasive nature. There is a need for an accurate, noninvasive blood-based molecular IVD test.

Methods: We randomized 572 PAX-RNA blood samples from two prospective, multicentre clinical studies. CRC cases originated from the MSKK study, controls from the CRC.SCR.2 study which enrolled healthy individuals from a screening population undergoing colonoscopy. Blood was drawn prior to surgery or prior to colonoscopy. RNA was isolated, QC checked, hybridized onto the Affymetrix U133 2.0 Plus arrays, and QC checked. Clinical data were monitored.

Results: After all QCs data of 462 pts remained. Data from 119 pts (55 cases, 64 controls) were utilized for discovery of gene signatures using a double nested bootstrap with random forest and SVM as feature selection methods. The best signature, Detector-C, discriminating between cases and controls contained 202 probe sets and resulted in a prospective sensitivity (S+) of 85.3% and a prospective specificity (S-) of 93.3%. The hypothesis for the prospective performance evaluation (validation) of Detector-C was to show a S+ of >70% and a S- of >80% with a one-sided alpha of 2.5% and a power of 97.5%. In order to test this hypothesis at least 122 cases and at least 109 controls would be needed. We used the remaining 210 cases and 133 controls for the prospective validation. S+ was 90% (95% CI: 0.851–0.937) and S- was 88% (95% CI: 0.812–0.930). S+ by UICC stage was: stage I: 0.89 (95% CI: 0.774–0.958), stage II: 0.90 (95% CI: 0.788–0.961), stage III: 90% (95% CI: 0.805–0.959) and stage IV: 93% (95% CI: 0.765–0.991). Detector-C also identified high-grade intraepithelial neoplasia with S+ of 66%. Multivariate analysis showed no significant effect of stage, age, gender, tumor localization, or RNA quality on correct prediction.

Conclusions: Detector-C measures the host response (host defense, immune answer, wound healing, inflammation) of white blood cells to tumor lesions and is highly suited for screening of CRC due its easy of use, noninvasiveness and its high sensitivity for early-stage CRC/neoplastic lesions.