Fig. 6: RAS Activity Pan-cancer.
From: RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma
a RI plotted per patient across the TCGA pan-cancer cohort. RNA-Seq gene counts were VST and z-score normalised per cohort. RAS mutants are highlighted (KRAS in red, HRAS in blue and NRAS in orange). Relative RAS isoform mutation frequencies per cohort are shown in the barchart to the right using the same colours. Frequencies of patients with a RAS gene amplification but no mutation are shown in grey. b A violin plot showing the distribution of mean RI across each TCGA cohort. The dotted orange line indicates the distribution minima separating the two cancer populations. c The ratio of patients with one or more RAS pathway mutations plotted against the mean RI for each cohort. A linear regression fit is shown in blue with a 99% confidence interval shown by the grey ribbon (spearman coefficient 0.432, p-value 0.014). Highly RAS active tumours are shown in red, BRAF-driven tumours in orange and tumours with a RI value below the lower 99% CI are shown in blue. d Boxplots showing distributions of RI values for pan-RAS mutant and wild-type patients. Significant cohorts are shown (linear model, for n see Supplementary Data 10; ****P ≤ 0.0001, ***P ≤ 0.001, **P ≤ 0.01, n.s.= P > 0.05). The box shows the median and IQR, the whiskers indicate ± 1.5 x IQR, outliers lie outside this range. e Boxplots showing distributions of RI values for THCA and SKCM split by BRAF mutation status (linear model fit THCA 281 mut, 192 wt; SKCM n = 180 mut, 180 wt; ****P ≤ 0.0001, ***P ≤ 0.001, **P ≤ 0.01, n.s.= P > 0.05). The box shows the median and IQR, the whiskers indicate ± 1.5 x IQR, outliers lie outside this range. f, g Kaplan–Meier plot showing a Cox proportional hazards regression fit of TCGA PAAD (f) or CESC (g) cohort survival data to corresponding RI values. The grey survival curve shows the observed data. The blue survival cure is the predicted survival if the RI values decreased 2-fold. The red curve are the predicted survival values if the RI were to increase 2-fold (coxph p-value 0.021 and 0.018, respectively).
