Fig. 2: Integrative omics analyses of melanoma samples.

a Venn diagram depicted the cascading effects of CNAs of cancer-associated genes (CAGs) in melanomas. The overlap between significant cis events across transcriptome and proteome are shown. b The volcano plot showed the copy number alteration predictive of OS in melanomas. c The heatmap represented the 18 survival associated CAGs which show significant correlation with copy numbers (CNs), mRNAs, or proteins. d The heatmap showed the correlation between CNs, mRNAs, and proteins of PRKDC. Samples are ranked from lowest (left) to highest (right) copy number values of PRKDC. e Kaplan–Meier curves for OS based on patients’ CNV status (log-rank test) in our cohort and TCGA cohort. f The forest plot showed the 95% CI of hazard ratio coefficients from Cox-regression for PRKDC amplification, and other covariates based on our cohort. g GSEA plots for DNA mismatch repair related pathways in PRKDC amplification vs WT comparisons. h Spearman-rank correlation of the PRKDC protein expression, and GSVA scores of DNA repair process. i The volcano plot showed the expression of proteins correlated with PRKDC copy numbers and predictive of OS in melanomas. j The comparison of the mRNA expression of ATM, and PRKDC between patients harboring PRKDC amplicons and WT samples in TCGA cohort (n = 267) (Wilcoxon rank test). k The comparison of the kinase activity of ATM, and PRKDC between patients harboring PRKDC amplicons and WT samples in our cohort (n = 96) (Wilcoxon rank test). l Dose–response curves of PRKDC inhibitor were determined on day 2 after inhibitors adding in PDCs from melanoma patients with or without SBS7a mutation signature. The data represent the mean values ± SD (n = 3) (left). The volcano plot showing the half-maximal inhibitory concentration (IC₅₀) scores. The data represent the mean values ± SD (n = 3) (right). m Proliferation of the PDCs from melanoma patients with and without SBS7a mutation signature based on the use of PRKDC inhibitor or control (two-way ANOVA followed by Tukey’s multiple comparison test). The data are presented as mean ± SEM, *p < 0.05; **p < 0.01; ***p < 0.001. n Proliferation of the PDCs from melanoma patients with or without PRKDC amplification based on the use of PRKDC inhibitor and 5-fluorouracil (5-FU) or control (two-way ANOVA followed by Tukey’s multiple comparison test). The data are presented as mean ± SEM, *p < 0.05; **p < 0.01; ***p < 0.001.