Figure 4. Genomic characterization of colon cancer according to the CMS classification.

(A) Arm-region frequencies of 309 colon cancer samples using CNApp default thresholds for CNAs. (B) BCS distribution by CMS sample groups (Figure 4—source data 1). FCS distribution by CMS sample groups is presented in Figure 4—figure supplement 1C. Wilcoxon rank-sum test significance is shown as p-value≤0.001 (***); p-value≤0.01 (**); p-value≤0.05 (*); p-value>0.05 (ns). (C) Number of gained and lost chromosome arms for each sample distributed according to the BCS values. Note that a cutoff at four is indicated with a black line. Annotation tracks for microsatellite instability (msi), BRAF mutated samples (braf_mut), CMS groups (cms_label), FCS and BCS are displayed. (D) Genome-wide profiling by chromosome arms distributed according to the CMS group. Annotation tracks for microsatellite instability (msi), BRAF mutated samples (braf_mut), CMS groups (cms_label), FCS and BCS are displayed. Sample-to-sample correlation heatmap plot by Pearson’s method is shown below. (E) Differentially altered chromosome arm regions between CMS groups (CMS1, CMS2, CMS3 and CMS4). Heatmap plot displaying the significance between CMS groups paired comparisons. Student’s T-test was applied and multiple testing correction by BH method was used to assess differences in chromosome arm values between groups. Adjusted p-values are displayed.

Figure 4—figure supplement 1. Genomic analysis of the COAD cohort.

(A) Kaplan-Meier survival analysis across CMS groups for overall survival (see Materials and methods section for clinical data extracted from TCGA data portal). (B) CNA profile bar plot with CNA alterations frequencies of 462 colon adenocarcinoma (TCGA-COAD cohort) and 164 rectum adenocarcinoma (TCGA-READ) samples using CNApp default thresholds (read for gains and blue for losses). (C) Box plot showing the distribution of FCS according to the CMS groups for 309 colon adenocarcinoma samples (Figure 4—figure supplement 1—source data 1). Wilcoxon rank-sum test was performed for each pair of groups to assess significant differences. Significance is expressed as: p-value≤0.001 (***); p -value ≤ 0.01 (**); p -value ≤ 0.05 (*); p -value > 0.05 (ns). (D) BCS values density plot for MSI (brown) and MSS (green) sample groups after Classifier model section implementation selecting BCS as classifier variable (N = 297 colon cancer samples). Vertical blue line at BCS = 4.75, as interception value between groups. (E) Sensitivity and specificity curves in ROC analysis across BCS threshold values showing the intersection value of 3.75 (green vertical line). The blue line shows our proposed threshold of BCS = 4. (F) Distribution of chromosome arm 20q copy-number amplitude values according to the CMS groups. Wilcoxon rank-sum test was performed for each pair of groups to assess significant differences. Significance is shown as p-value≤0.001 (***); p-value≤0.01 (**); p-value≤0.05 (*); p-value>0.05 (ns). (TIFF 664 KB).