Fig. 5: Wild-type Kras deletion increases tumour initiation and alters progression of KRASG12D mutant colorectal tumours following loss of p53. | Nature Communications

Fig. 5: Wild-type Kras deletion increases tumour initiation and alters progression of KRASG12D mutant colorectal tumours following loss of p53.

From: KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo

Fig. 5

a Kaplan–Meier survival curve of villin-creERT2 Kras+/G12D and Krasfl/G12D mice aged until clinical endpoint (Kras+/G12D, n = 16, 5M, 11F; Krasfl/G12D, n = 12, 4M, 8F). ****P = 1.3 × 10-9. MS, median survival. b Dotplot showing total number of tumours from Kras+/G12D and Krasfl/G12D 2D mice. Data are mean ± s.e.m. (Kras+/G12D, n = 11, 3M, 8F; Krasfl/G12D, n = 11, 4M, 7F). **P = 0.0014. c Representative H&E and BrdU IHC images of Krasfl/G12D mice. Representative of 6 biological replicates per genotype. Dashed boxes highlight selected areas shown in high magnification. Scale, 200 µm. d Metacore Network analysis of differentially expressed genes from Krasfl/G12D tumours. e Geneset enrichment plot for Wnt beta-catenin signalling signature from the ‘Hallmark’ geneset collection of tumours derived from Krasfl/G12D mice. X-axis shows normalised enrichment score (NES), and the P value (computed and corrected for multiple testing using the Benjamini–Hochberg procedure). f Representative β-catenin IHC staining in Kras+/G12D and Krasfl/G12D mice. Representative of 5 biological replicates per genotype. Dashed boxes highlight selected areas shown in high magnification. Scale, 200 µm. g Kaplan–Meier survival curve of Kras+/G12D Trp53fl/fl (KP) and Krasfl/G12D Trp53fl/fl (KP KF) mice aged until clinical endpoint (KP, n = 10, 7M, 3F; KP KF, n = 16, 6M, 10F) ****P = 6 × 10-8. h Boxplots showing total number of tumours (left) and tumour burden, mm2 (right) in KP and KP KF mice (KP, n = 7, 2M, 5F, KP KF, n = 15, 6M, 9F). *P = 0.02, **P = 0.0017. Please note control KP cohort used in (g) and (h) comprise different mice. i Representative H&E, αSMA (alpha-smooth muscle actin) and Sirius Red staining of KP and KP KF tumours. Representative of KP n = 8; KP KF n = 5. Scale, 100 µm. j Boxplots showing Sirius Red positivity (%) and αSMA positive cells (%) of KP and KP KF tumours (KP n = 7; KP KF, n = 5). *P = 0.0326 (Sirius Red), *P = 0.024 (αSMA). h and j boxes depict interquartile range, central line indicates median and whiskers indicate minimum/maximum values. P values in a and g are log-rank (Mantel-Cox) tests. b, h and j are one-way Mann–Whitney U tests. Source data are provided as a Source Data file.

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