Figure 6From: Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancerBoth human CRCs and mouse colon tumors reactivate an embryonic gene signature. When human and murine tumors are compared, they both broadly re-express an embryonic gene expression pattern. Gene expression profiles from the mouse tumor models and human CRC samples were combined into a single non-redundant gene ortholog genome table structure and subjected to comparative profile analysis. Informative probe-sets from human and mouse platforms were selected, mapped to corresponding ortholog genes, and used to populate a table in which normalized expression for each gene is relative to normal adult colon. (a) Heatmap plot for all cross-species gene orthologs both present and successfully measured on both the Affymetrix Hg-U133 and Vanderbilt Mouse NIA 20 K microarrays (n = 8,621 features). This representation suggests that a large number of human CRC signatures exhibit similar behaviors in the mouse tumors and during embryonic mouse colon development (sidebar: 1,080 (red) and 431 (green) gene lists from (b)). (b) Based on results in (a), four separate gene lists were generated with criteria of over- or under-expression in development or over-expression or under-expression in human CRCs (2,718, 2,365, 2,212, and 737, respectively, with the overlaps shown as a sidebar in (a); red, 1,080 transcripts, and green, 431 transcripts). Genes over-expressed and under-expressed in embryonic mouse colon and human CRCs were found to be over-represented as determined by Fisher's exact test analysis (*p < 7 × 10-88, **p < 1 × 10-76, ***p < 5 × 10-4, ****p < 1 × 10-76). (c) Heatmap plot of all genes co-regulated in human CRCs and during early (ED) and late (LD) mouse embryonic colon development (n = 2,216 features). Six predominant clusters (C18-C23) characterize the transcriptional relationship between human CRC and mouse colon tumor models and embryonic development. Two clusters (C20 and 21) primarily distinguish human CRCs from murine tumors (A, M, S and T). For example, CRC up-regulated transcripts that are either developmentally up- or down-regulated are represented by cluster C22 (n = 860 features) and clusters C21/C23 (n = 142 features), respectively. Conversely, CRC down-regulated transcripts that are either down- or up-regulated during development are shown in clusters C18/C19 (n = 258 features) and cluster C20 (n = 42 features), respectively. Interestingly, while approximately 80% and approximately 60% of genes up- and down-regulated in both human CRCs and mouse development were also up- and down-regulated in tumors from the various mouse models, several clusters provide very interesting exceptions: cluster C20 comprises genes down-regulated in human CRCs that are routinely over-expressed in mouse tumors and development; cluster C21 comprises genes robustly expressed in human CRC that are rarely expressed in embryonic colon or murine tumors. Sample groups: ED, early development (E13.5-E15.5); LD, late development (E16.5-E18.5); A, AOM-induced; M, ApcMin/+; T, Tgfb1-/-; Rag2-/-; S, Smad3-/-. Tissue groups: AC, adult colon; CRC, human CRC. Staging: nAC, normal colon.Back to article page