Expression intensity in normal compared to tumor samples. Colon adenocarcinoma samples and paired normal samples were hybridized to GeneChips, (Affymetrix) and the expression levels were analyzed with GeneChip 3.0 analysis software (Affymetrix). The upper and lower boundaries represent a 4-fold difference in the average of each genes expression between carcinoma and normal tissue. Closed circles denote genes for which average expression in carcinoma was significantly higher or lower than it was in the matched normal sample (p<0.001). Approximately 2 % of the 4000 genes analyzed for this figure displayed a statistically significant, 4-fold difference in expression intensity between tumor and matched normal samples. Data from the adenoma samples are not included in this figure.
Comparison of transcript expression levels in individual neoplasms (adenoma and adenocarcinoma) with paired normal tissue samples. Figure 1(a): transcripts with decreased expression in tumors. Figure 1(b): transcripts with increased expression in tumors. For each transcript, the mean ratio of expression in neoplasm to normal tissue and normal was 4-fold or greater (p<0.001). The ordinate scale is logarithmic. Due to the adjustment of transcripts with an intensity < 10 to 10, data points may superimposed, and visualized as a single data point. However, for each transcript the number of samples was the same. Ca, Carcinoma (N = 18); Ad, Adenoma (N = 4); Ca-Nl, normal paired with carcinoma (N = 18); Ad-Nl, normal paired with adenoma (N = 4).
Cluster map and phylogenetic tree resulting from a two-way pair-wise average-linkage cluster analysis. Approximately 1800 genes in common to two versions of GeneChip (Affymetrix) were combined into a single matrix that was then clustered as described in the text. Each color patch in the resulting visual map represents the expression level of the associated gene in that tissue sample, with a continuum of expression levels from dark green (lowest) to bright red (highest). Missing values are coded as silver. The carcinomas and their benign precursors, the adenomas, are placed on an entirely different trunk than are the paired normal tissues. Strikingly, the adenomas and the carcinomas are also separated from one another, occupying adjacent branches of the same trunk. The color map indicates that this hierarchy is associated with several distinct groupings of increased gene expression intensity (Clusters 1 3).
Upper panel, Cluster 1:A cluster of genes that are more intensely expressed in adenoma than in normal tissue or carcinoma. This grouping contained approximately 8-10 genes whose mRNA expression appeared to be much higher in the adenoma samples than in associated normal tissue or the carcinomas.
Lower panel, Cluster 2: A cluster of genes that are more highly expressed in carcinoma than in adenoma or normal tissue. This is a broad and diffuse cluster, which contains many products that were also identified simply by examining expression ratios (Table 1).
Expression ratios in cancer compared with adenoma for the subset of genes which were dysregulated in cancer.