641 Transcriptomic and bioinformatic evidence for disctict roles of p38 isoforms in cutaneous melanoma

The p38 kinases mediate cell adaptation to stresses and play varying roles in tumorigenesis. However, the isoform-specific cutaneous melanoma (SKCM), particularly context of clinically important driver mutations, remain elusive. We used bioinformatic tools analyze isoform expression TCGA SKCM subtypes defined by presence BRAF or NRAS mutations. found that p38β, p38γ p38δ levels were increased, while p38α decreased BRAF-mutated (MT) compared wild-type (WT) metastatic SKCM. In contrast, was NRAS-MT relative NRAS-WT None these correlations significant primary negatively correlated, positively correlated with CD8+ T B abundance across BRAF- Moreover, biomarkers for cells, cell, dendritic other immune populations, as well exhaustion markers subtypes. positive correlation may have implications potential prospect targeting TME boost antitumor immunity. protein-protein interaction network analysis revealed top-ranked p38γ-interacting genes SNTA1 ROBO1 known promote cancer migration angiogenesis, respectively. Interestingly, p38δ-interacting gene GPX4 is MT resistance inhibitors. Notably, based on drug sensitivity analysis, high 15 drugs small molecules, including inhibitor. summary, our data support distinct p38s different genomic at disease progression stages, raising possibility a more individually tailored approach treatment