Molecular Staging for Survival Prediction of Colorectal Cancer Patients

Authors:
  • IYIvana Yang
    Ivana Yang
  • GBGreg Bloom
    Greg Bloom
  • KKKa Yin Kwong
    Ka Yin Kwong
  • DBDavid Boulware
    David Boulware
  • ACAlan Cantor
    Alan Cantor
  • DCDomenico Coppola
    Domenico Coppola
  • MKMogens Kruhøffer
    Mogens Kruhøffer
  • TOTorben F. Orntoft
    Torben F. Orntoft
  • TYTimothy J. Yeatman
    Timothy J. Yeatman
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Abstract
Purpose: The Dukes' staging system is the gold standard for predicting colorectal cancer prognosis; however, accurate classification of intermediate-stage cases is problematic. We hypothesized that molecular fingerprints could provide more accurate staging and potentially assist in directing adjuvant therapy. Methods: A 32,000 cDNA microarray was used to evaluate 78 human colon cancer specimens, and these results were correlated with survival. Molecular classifiers were produced to predict outcome. Results: Molecular staging, based on 43 core genes, was 90% accurate (93% sensitivity, 84% specificity) in predicting 36-month overall survival in 78 patients. This result was significantly better than Dukes' staging (P = .03878), discriminated patients into significantly different groups by survival time (P < .001, log-rank test), and was significantly different from chance (P < .001, 1,000 permutations). Furthermore, the classifier was able to discriminate a survival difference in an independent test set from Denmark. Molecular staging identifies patient prognosis (as represented by 36-month survival) more accurately than the traditional clinical staging, particularly for intermediate Dukes' stage B and C patients. The classifier was based on a core set of 43 genes, including osteopontin and neuregulin, which have biologic significance for this disease. Conclusion: These data support further evaluation of molecular staging to discriminate good from poor prognosis patients, with the potential to direct adjuvant therapy.

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