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. 2023 Jul 31;4(9):1292–1308. doi: 10.1038/s43018-023-00610-2

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© The Author(s) 2023, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a, Left, schematic representation of the discovery cohort. Right, volcano plot showing the difference in BRAF-WT (n = 79 V600-negative samples)- and BRAF-mutant (n = 77 V600-positive samples)-associated gene expression (log₂ (values)) and q values (−log₁₀ (adjusted P values) from multiple unpaired t-tests with Benjamini, Krieger and Yekutieli test correction) in the discovery cohort. Each dot represents a gene; significant differentially expressed genes (q < 0.05) are shown in a color-coded manner. b, Heatmap showing enrichment scores (−log₁₀ (adjusted P values), Benjamini–Hochberg-corrected FDR) of functional pathways in Wiki, Reactome and KEGG pathway databases. c, Scatter dot plots showing gene expression of IL17A and IL17B (n = 79 BRAF-WT, n = 77 BRAF-mutant tumors). Dots represent biologically independent patient samples. Mean ± 95% CIs are plotted; P values are from the unpaired t-test. d, Stacked bar plot showing the number of patients according to IL-17 signaling GES (according to KEGG hsa04657; cut point at median) and mutational subgroups in the TCGA-SKCM cohort (n = 363 tumor tissues). The P value is from the χ² test. e, Scatterplot showing the correlation between IL-17 and the PROGENy MAPK activation GES in the TCGA-SKCM cohort (n = 363 tumor tissues). The line is from linear regression ±95% CI bands. f, Kaplan–Meier plot for OS according to the IL-17 signaling GES (KEGG hsa04657) in the TCGA-SKCM cohort. g–l, Kaplan–Meier plots for PFS (g–i) and OS (j–l) according to the IL-17 family GES (‘IL-17A–IL-17F GES’, IL-17 family cytokines containing the six structurally related cytokines) in patients treated with dual-ICI (g,j), mono anti-CTLA-4 (h,k) and mono anti-PD-1 (i,l) therapy. g–l, HR and 95% CIs are reported for high-expression groups. P values were calculated with the log-rank test. Categorization into ‘high’ versus ‘low’ was done according to an optimal cut point. All P values are two tailed. mt, mutant; FFPE, formalin fixed, paraffin embedded; BL, baseline; NS, not significant; NOD, nucleotide-binding oligomerization domain; assoc., associated; α, anti; N/A, not available.

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