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. 2025 Apr 6;44(25):2091–2102. doi: 10.1038/s41388-025-03365-5

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© The Author(s) 2025

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

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Fig. 4 — a CDX2 levels in MSS patients, n = 839. Violin plot displays median and quartiles. b Comparison of CDX2 expression in 2 groups based on APC and CTNNB1 mutational status. WT = wildtype, n = 151. mutant, n = 688. Dots represent individual patients. Data analyzed with unpaired two-tailed Student’s t test. c Comparison of APC/CTNNB1 mutational status in 2 groups based on CDX2 expression levels (25% highest vs 25% lowest expressors). N = 210 for both groups. Percentages are normalized within each group. Data analyzed with Fisher’s exact test. d Comparison of APC/CTNNB1 mutational status in 2 groups based on CMS classification. CMS1/23; n = 431, CMS4; n = 255. Percentages are normalized within each group. Data analyzed with Fisher’s exact test. e CMS distribution within 25% of patients with highest CDX2 levels versus CMS distribution within 25% of patients with lowest CDX2 levels. N = 210 for both groups. Data analyzed with Fisher’s exact test. f Confusion matrix calculated for iCMS2 or iCMS3 score within CMS4 patients. Groups are based on 25% highest CDX2 expressors within CMS4 patients, mutant for APC/CTNNB1 (n = 61, 58 iCMS classified and 3 patients undefined for iCMS classification) or on 25% lowest CDX2 expressors within CMS4 patients, WT for APC/CTNNB1 (n = 30, 26 iCMS classified and 4 patients undefined for iCMS classification). Data analyzed with Fisher’s exact test. g Kaplan-Meier curve for overall survival calculated for groups based on 25% highest CDX2 expressors within CMS4 patients, mutant for APC/CTNNB1 (n = 61) or on 25% lowest CDX2 expressors within CMS4 patients, WT for APC/CTNNB1 (n = 30). Data analyzed by Logrank test. h Pie charts comparing the percentage incidence of metastasis in all CMS4 patients (left) versus subsets of CMS4 patients; APC/CTNNB1 mutant samples within 25% highest CDX2 expressors (middle) versus APC/CTNNB1 WT samples within 25% lowest CDX2 (right). Percentages are normalized within each group. CMS4 patients, n = 255; APC/CTNNB1 mutant 25% highest CDX2 expressors CMS4, n = 61; APC/CTNNB1 WT 25% lowest CDX2 expressors CMS4, n = 30. Difference between 25% highest and lowest expressors analyzed with Fisher’s exact test. R version 4.3.2 was used for statistical analyses.