1. ¹Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus N DK8200, Denmark
2. ²Department of Pathology, Aarhus University Hospital, Aarhus DK8000, Denmark
3. ³Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands
4. ⁴Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg D-20246, Germany
5. ⁵Department of Medical Genetics, Biomedicum, University of Helsinki, Helsinki FI 00290, Finland
6. ⁶Department of Surgery, Aarhus University Hospital, Aarhus DK8000, Denmark

Correspondence: Professor TF Ørntoft, E-mail: orntoft@ki.au.dk

Received 1 October 2008; Revised 15 December 2008; Accepted 16 December 2008; Published online 20 January 2009.

Abstract

The aim of this study was to identify deregulated transcription factors (TFs) in colorectal cancer (CRC) and to evaluate their relation with the recurrence of stage II CRC and overall survival. Microarray-based transcript profiles of 20 normal mucosas and 424 CRC samples were used to identify 51 TFs displaying differential transcript levels between normal mucosa and CRC. For a subset of these we provide in vitro evidence that deregulation of the Wnt signalling pathway can lead to the alterations observed in tissues. Furthermore, in two independent cohorts of microsatellite-stable stage II cancers we found that high SOX4 transcript levels correlated with recurrence (HR 2.7; 95% CI, 1.2–6.0; P=0.01). Analyses of 1000 stage I–III adenocarcinomas, by immunohistochemistry, revealed that patients with tumours displaying high levels of CBFB and SMARCC1 proteins had a significantly better overall survival rate (P=0.0001 and P=0.0275, respectively) than patients with low levels. Multivariate analyses revealed that a high CBFB protein level was an independent predictor of survival. In conclusion, several of the identified TFs seem to be involved in the progression of CRC.