摘要：

This study demonstrates the successes and challenges of prognostic and predictive marker validation in a rapidly advancing field. From a set of 295 initially tested genes, a panel of 72 genes was used to approximately characterize tumors according to a their similarity, on genes that overlapped, to a previously published classification system, the Colorectal Cancer Assigner (CRCA). The activity of oxaliplatin was then assessed in the 5 distinct CRCA subtypes (enterocyte, goblet-like, inflammatory, stemlike, and transit amplifying) in a discovery and validation set. Importantly, the 295 genes tested (of which 72 were used to define the subtype classification) were selected in part based on their prognostic and predictive ability in the NSABP C-07 training set. Thus the fact that the approximate CRCA classification identified apparently strong oxaliplatin benefit in 1 subgroup in the initial discovery analysis (patients with enterocyte tumors) that could not be confirmed in the validation cohort is not wholly surprising. More convincing is the clear demonstration in the validation set of the prognostic importance of several gene expression–based classification schemes. Stemlike tumors were consistently associated with poor prognosis independent of tumor stage. These tumors might be considered appropriate for clinical trials testing experimental approaches, since their outcome is poor with standard adjuvant chemotherapy.

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