Overall deregulation in gene expression as a novel indicator of tumor aggressiveness in colorectal cancer.

Malignant transformation of the cell is accompanied and characterized by disruption of genetic material and aberrant expression of multiple genes. Systematic analysis of differential gene expression in human tumor samples may provide an estimate of the degree of genetic and epigenetic deregulation in neoplastic cells. We have assessed, by means of a RNA differential display technique, the overall gene expression deregulation in a prospectively collected series of 68 human colorectal carcinomas. An index of differential expression has been calculated for each case. A similar proportion of the displayed sequences (23%) was under- and over-represented in the tumor in respect of the normal tissue. An increased variation in the expression profile was observed in advanced Dukes' stages (P < 0.02) and correlated with lymph node invasion (P < 0.05). Furthermore, a diminished overall survival was associated to increased rates of deregulation (Log-rank, P < 0.02) and especially down-regulation (P < 0.001). When Cox multivariate analysis was performed in front of Dukes' stage, both indexes of differential expression were independent indicators of a worse outcome (P = 0.05 and P < 0.01 respectively). We conclude that estimation of the fraction of differentially displayed tags by RNA fingerprinting may have relevant applications in the prognostic assessment of colorectal cancer.