Gene Expression Profiling of Nonneoplastic Mucosa May Predict Clinical Outcome of Colon Cancer Patients.

Autor: Barrier, Alain, Boelle, Pierre-Yves, Lemoine, Antoinette, Tse, Chantal, Brault, Didier, Chiappini, Franck, Lacaine, François, Houry, Sidney, Huguier, Michel, Flahault, Antoine, Dudoit, Sandrine
Zdroj: Diseases of the Colon & Rectum; Dec2005, Vol. 48 Issue 12, p2238-2248, 11p, 1 Color Photograph, 3 Graphs
Abstrakt: PURPOSE: This study assessed the possibility to build a prognosis predictor, based on microarray gene expression measures, in Stage II and III colon cancer patients. METHODS: Tumor and nonneoplastic mucosa mRNA samples from 12 colon cancer patients were profiled using the Affymetrix HGU133A GeneChip. Six of 12 patients experienced a metachronous metastasis, whereas the 6 others remained disease-free for more than five years. Three datasets were constituted, including, respectively, the gene expression measures in tumor samples (T), in adjacent nonneoplastic mucosa samples (A), and the log-ratio of the gene expression measures (L). The step-down procedure of Westfall and Young and the k-nearest neighbor class prediction method were applied on T, A, and L. Leave-one-out cross-validation was used to estimate the generalization error of predictors based on different numbers of genes and neighbors. RESULTS: The most frequent results were one false prediction with the A-based predictors (95 percent) and two false predictions with the T- and L-based predictors (65 and 60 percent, respectively). A-based predictors were more stable (i.e., less sensitive to changes of parameters, such as numbers of genes and neighbors) than T- and L-based predictors. Informative genes in A-based predictors included genes involved in the oxidative and phosphorylative mitochondrial metabolism and genes involved in cell-signaling pathways and their receptors. CONCLUSIONS: This study suggests that one can build a prognosis predictor for Stage II and III colon cancer patients, based on microarray gene expression measures, and suggests the potential usefulness of nonneoplastic mucosa for this purpose. [ABSTRACT FROM AUTHOR]
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