Research on the influence of radiotherapy-related genes on immune infiltration, immunotherapy response and prognosis in melanoma based on multi-omics.

BACKGROUND: Skin cutaneous melanoma (SKCM) is a significant oncological challenge due to its aggressive nature and poor treatment outcomes. This study explores the comprehensive effects of radiotherapy (RT) in SKCM, focusing on cell signaling pathways, immune infiltration, immune gene correlations, immunotherapy response, and prognosis. METHODS: Using the Cancer Genome Atlas (TCGA) database, differentially expressed genes (DEGs) in SKCM patients undergoing RT were identified. A risk score model based on these DEGs was developed to assess the effects of RT-related genes on drug sensitivity, immune cell infiltration, immunotherapy response, and prognosis through multi-omics analysis. Human melanoma cells UACC62 and UACC257 were irradiated with 8 Gy gamma ray to establish an in vitro model, verifying the impact of radiotherapy on gene expression. RESULTS: The risk score demonstrated significant prognostic value and emerged as an independent prognostic factor. miRNA-mRNA and transcription factor regulatory networks underscored its clinical significance. Four key genes were identified: DUSP1, CXCL13, SLAMF7, and EVI2B. Analysis of single-cell and immunotherapy datasets indicated that these genes enhance immune response and immunotherapy efficacy in melanoma patients. PCR results confirmed that gamma rays increased the expression of these genes in human melanoma cells UACC62 and UACC257. CONCLUSION: Using a multi-omics approach, we analyzed and validated the impact of RT on the immune landscape of melanoma patients. Our findings highlight the critical role of RT-related genes in predicting SKCM prognosis and guiding personalized therapy strategies, particularly in the context of immunotherapy. These contribute to understanding the role of radiotherapy combined with immunotherapy in melanoma.