Stage III colon cancer prognosis prediction by gene expression profiling

A. Barrier,P. Boelle, D. Brault, S. Houry, F. Lacaine,A. Flahault,S. Dudoit,A. Lemoine

Journal of Clinical Oncology(2007)

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摘要
10590 Background and Aims: Postoperative chemotherapy has become part of the standard treatment for stage III colon cancer patients. Since approximately half of patients are cured by surgery alone, adjuvant chemotherapy should not be used in all patients. This study aimed to assess the possibility to use microarray-based gene expression profiles to predict the prognosis of stage III colon cancer patients. Material and Methods: Forty-two patients operated on for a stage III colon cancer were included in this study. Twenty-one patients have received an adjuvant chemotherapy, while the other 21 have received no treatment. Twenty patients have developed a liver metastasis, while the other 22 have remained disease-free for at least 5 years. Tumor mRNA samples were profiled using the Affymetrix HGU133A GeneChip. Two analyses were performed: one with the 42 patients, the other with the 21 patients who did not receive any adjuvant chemotherapy. For each analysis, patients were repeatedly and randomly divided into 10,000 training (TS) and validation sets (VS) of 10 different sizes. For each TS/VS split, a 30-gene prognosis predictor (PP), identified on the TS, was used to predict the prognosis of VS patients. Performances of a 15-gene PP and a 34-gene PP, proposed by another research team, were also assessed on the same TS and VS. Results: First analysis (42 patients). The 10,000 30-gene PP yielded the following average prognosis prediction performance measures: 73.8% accuracy, 74.6% sensitivity, and 73.0% specificity. Improvements in prognosis prediction were observed with increasing TS size. A total of 4,446 genes were included in the 10,000 PP. The 15-gene PP yielded a 69.7% accuracy; the 34-gene PP yielded a 71.2% accuracy. Second analysis (21 patients). The 10,000 30-gene PP yielded the following average prognosis prediction performance measures: 77.7% accuracy, 75.8% sensitivity, and 79.9% specificity. Improvements in prognosis prediction were observed with increasing TS size. A total of 5,478 genes were included in the 10,000 PP. The 15-gene PP yielded a 78.5% accuracy; the 34-gene PP yielded a 81.9% accuracy. Conclusion: Microarray gene expression profiling is able to predict the prognosis of stage III colon cancer patients and, thus, might be used for an appropriate use of adjuvant chemotherapy. No significant financial relationships to disclose.
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