Genomic and transcriptomic prognostic factors in R0 Dukes B and C colorectal cancer patients

Abstract

The advent of various 'omic' technologies has increased expectations in the field of biomarkers. In an attempt to clarify how different strategies may contribute to improving prognostic classification and to identify new predictors of patient outcome we analyzed genomic and transcriptomic profiles in a series of R0 Dukes B and C colorectal carcinomas. We have compared the predictive capability of each approach against conventional clinicopathological and molecular parameters. At a genomic level, gains at 11q including amplification at 11q13 were an indicator of poorer outcome. In transcriptomic analyses we identified 68 genes whose expression levels correlated with survival (p<0.01) and included overexpression of WASF1, NFE2L2, and MMP9, and underexpression of ITGAL, TSC2, and SDF2. Gene expression levels paralleled chromosomal changes only in 56% of the genes, suggesting that, as a general trend, the direct effect of chromosomal copy number changes on gene expression levels is minimal. Classification of tumors by genomic and transcriptomic signatures resulted in non-overlapping subgroups and was not of prognostic value. We conclude that genomic and transcriptomic profiling of colorectal carcinomas may contribute as novel prognostic markers, but it does not improve outcome prediction when global profiles or signatures are considered.