Figure 4. Conserved Notch signatures in both mouse and human intestinal tumors.

(A) Heat map comparison between Notch-responsive genes (clusters A and B in Figure 3A) from mouse models and microarray data sets from human CRC patients (GEO GSE5206 and GSE2109). Note that genes upregulated upon Notch activation in Apc^min tumors have higher expression levels in Nrarp^hi tumors compared with those of Nrarp^lo tumors and vice versa. Asterisk indicates the group of genes that do not correlate between mouse and human data. APC, Vil-Cre;Apc^min. (B) Positive correlation of CDX1 and CDX2 (transcription factor for epithelial differentiation) and negative correlation of VIMENTIN (epithelial-mesenchymal transition marker) and PROX1 (tumor progression related gene) with Nrarp, respectively. ρ, correlation coefficient. Statistics are by Pearson’s correlation. (C) Expression levels of Nrarp in the 3 independent microarray data sets (GEO GSE5206, GSE4107, and GSE 8671). AD, adenoma; AC, adenocarcinoma; WD, well differentiated; MD, moderately differentiated; PD, poorly differentiated; C, cancer. Note the reduced Nrarp expression in CRCs compared with normal tissue. ***P < 0.001; **P < 0.005. Statistics for far-left graph are by ANOVA. (D) Positive correlation between Nrarp expression and patient survival from microarray data set (GEO GSE17538). The Kaplan-Meier method was used to estimate survival of the 2 groups; Nrarp^hi (solid line) and Nrarp^mid/lo (dotted line).