Fig. 6

RC48 plus dabrafenib treatment affected additional pathways and downregulated unique melanoma-associated prognostic genes. A Heatmap showing the mRNA levels of the top 100 genes (50 downregulated or downregulated) after RC48 plus dabrafenib combination treatment. The expression levels of each gene were normalized to the total mRNA abundance of each sample and compared with that of vehicle-treated controls. B The top-ranked positively and negatively enriched gene sets identified using GSEA in response to combination treatment. GSEA was conducted with top common DEGs in A2058 cells after combinational treatment using 38 HALLMARK gene sets database in MSigDB. C GSEA plots showing strong negative enrichment of the MYC Targets v1, E2F_targets, and KRAS_signaling_up in A2058 cells in response to combination treatment. NES, normalized enrichment score; FDR, false discovery rate. D Kaplan–Meier estimate of overall survival based on expression of DEGs (TCGA melanoma Cohort). High relative expression of AIMP2, AURKA, AURKB, CDC45, CDCA3, CKS1B, HMGB3, KPNA2, MCM5, and NCAPD2 genes, and low relative expression of MAFB, NUPR1, and SLC1A3 were associated with poor overall survival in the melanoma cohort. The log rank (Mantel–Cox) test was used for significance, with p < 0.05 considered significant