Table 1.
Clinical characteristics of patients included in the training set.
Figure 1.
Identification of the 34-probe gene signature.
The CT/HM values for the 13 pairs of samples and the 34 probes identified using paired SAM analysis were plotted versus the CT/HN values obtained in one paired sample from Sheffer's study [7]. The horizontal axis and the diagonal (HM = HN) separate the graph in four quadrants. (a) Genes over-expressed in HM versus CT, and downregulated in HM versus HN. (b) Genes over-expressed in HM versus CT, and in HM versus HN. (c) Genes downregulated in HM versus CT, and over-expressed in HM versus HN. (d) Genes downregulated in HM versus CT, and in HM versus HN. The red dashed line corresponds to a simulated contamination of a CT sample with 50% of a HN sample (see equation 1 in results section). The hatched region corresponds to HM samples that either are expressed at a comparable level (less than a 2-fold difference) in HM and CT or HM and HN, or whose variation between CT and HM can be explained by a contamination of HM by HN.
Table 2.
Downregulated genes in hepatic metastases compared to the paired primary colon tumor.
Table 3.
Upregulated genes in hepatic metastases compared to the paired primary colon tumor.
Figure 2.
Hierarchical clustering of the samples collected in this study.
HMp and CTp are the 13 paired samples used to identify the 34-probe signature (Table 1). HMu, CTu and CNu are additional samples collected in this study (Table S1).
Table 4.
External validation.
Figure 3.
Hierarchical clustering of colon validation set.
Data collected, hybridized and normalized by Sheffer et al. [7] were clustered using our 34-probe signature.
Figure 4.
Expression of identified genes in three studies.
Datasets from three intendant studies were renormalized together using an empirical Bayes method. Among the 33 genes of the gene signature, 32 genes were present in our (red), Sheffer (green) and Kleivi (blue) datasets (Table 4). The log2 ratio of HM to CT is plotted. Genes were ordered from the most downregulated to the most upregulated gene in HM versus CT in our study.
Figure 5.
Functional annotation enrichment analysis of the 33-gene signature.
Gene Ontology terms significantly over-represented in the 33-gene signature were identified and plotted using ClueGO. A) The size of the nodes are inversely proportional to the pvalue in Fig. 5B. Line widths between GO terms are proportional to the kappa scores used to define the categories. B) Table giving the results of the ClueGO analysis. Nr: Number of genes in our 33-gene signature associated with the GO term.%: Percentage of the genes of the considered GO term presents in our signature. Pvalue: pvalue of the GO term, corrected for multiple testing. C) Relation between the GO annotations of the 11 “cell adhesion”-associated genes in Fig. 5B and GO:0007155 term. Black arrows: “is a”. Green arrows: “Positively regulates”.