Original Article
Oncogene (2007) 26, 2642–2648. doi:10.1038/sj.onc.1210060; published online 9 October 2006
Prognosis of stage II colon cancer by non-neoplastic mucosa gene expression profiling
A Barrier1,2,3,4, F Roser5,6,7, P-Y Boëlle2,3, B Franc8,9, C Tse3,10, D Brault3,10, F Lacaine1,3, S Houry1,3, P Callard3,11, C Penna9,12, B Debuire5,6,7, A Flahault2,3, S Dudoit4 and A Lemoine5,6,7
- 1Service de Chirurgie Digestive, Hôpital Tenon, AP-HP, Paris, France
- 2UMR S 707, INSERM, Paris, France
- 3Faculté de Médecine, Université Pierre et Marie Curie-Paris 6, Paris, France
- 4Division of Biostatistics, School of Public Health, University of California, Berkeley, CA, USA
- 5UMR S 602, INSERM, Villejuif, France
- 6Service de Biochimie, Hôpital Paul Brousse, AP-HP, Villejuif, France
- 7Faculté de Médecine, Université Paris 11, Villejuif, France
- 8Service d'Anatomie Pathologique, Hôpital Ambroise Paré, AP-HP, Boulogne Billancourt, France
- 9Faculté de Médecine, Université Versailles Saint Quentin, Boulogne Billancourt, France
- 10Service de Biochimie, Hôpital Tenon, AP-HP, Paris, France
- 11Service d'Anatomie Pathologique, Hôpital Tenon, AP-HP, Paris, France
- 12Service de Chirurgie Digestive, Hôpital Ambroise Paré, AP-HP, Boulogne Billancourt, France
Correspondence: Dr A Lemoine, Service de Biochimie, Hôpital Paul-Brousse, 12 Avenue Paul Vaillant Couturier, Villejuif cedex 94804, France. E-mail: antoinette.lemoine@pbr.ap-hop-paris.fr
Received 2 January 2006; Revised 5 July 2006; Accepted 6 September 2006; Published online 9 October 2006.
Abstract
We have assessed the possibility to build a prognosis predictor (PP), based on non-neoplastic mucosa microarray gene expression measures, for stage II colon cancer patients. Non-neoplastic colonic mucosa mRNA samples from 24 patients (10 with a metachronous metastasis, 14 with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. Patients were repeatedly and randomly divided into 1000 training sets (TSs) of size 16 and validation sets (VS) of size 8. For each TS/VS split, a 70-gene PP, identified on the TS by selecting the 70 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Mean prognosis prediction performances of the 70-gene PP were 81.8% for accuracy, 73.0% for sensitivity and 87.1% for specificity. Informative genes suggested branching signal-transduction pathways with possible extensive networks between individual pathways. They also included genes coding for proteins involved in immune surveillance. In conclusion, our study suggests that one can build an accurate PP for stage II colon cancer patients, based on non-neoplastic mucosa microarray gene expression measures.
Keywords:
functional genomics, colon cancer, prognosis prediction, non neoplastic mucosa, cross validation, cDNA arrays
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Prognosis of stage II colon cancer by non-neoplastic mucosa gene expression profiling
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