Prognostic value of tumor progression-related gene expression in colorectal cancer patients

Colorectal cancer (CRC) is driven by genetic alterations causing its progression. Besides accepted tumor suppressor- and onco- genes, a series of genes have been identified, which contribute to transformation into a more malignant stage. We investigated whether the expression level of such genes, alone or in combination, could add to predict the prognosis of CRC patients. Tumor samples from 118 CRC patients were screened in a retrospective analysis by qRT-PCR for expression of the four tumor progression-associated genes osteopontin (Opn), transforming growth factor beta (Tgf-beta), matrix metalloproteinase-2 (Mmp-2) and cyclooxigenase-2 (Cox-2). The resulting qRT-PCR values were related to those of housekeeping genes. All patients were clustered for similar expression levels between the four genes with R statistical software using the package pvclust, which provides bootstrap agglomerative hierarchical clustering. Clusters with similar expression of the four genes were analyzed for correlation with UICC stages and survival time. Expression of the four genes varied considerably within the cohort of patients. Cluster analysis of patients revealed a subgroup (n = 33) who in comparison with the other patients showed tenfold higher expression levels of all four genes (p < 0.001, respectively). However, there was no correlation between patients expressing high or low levels of these four genes and known parameters of clinical prognosis (UICC stages, survival time). In conclusion, tenfold increased expression levels of Opn, Tgf-beta, Mmp-2 and Cox-2 in a subset of CRC patients did not predict for a clinical outcome that is different from that of the remaining patients.