Immune Landscape and an RBM38-Associated Immune Prognostic Model with Laboratory Verification in Malignant Melanoma

SIMPLE SUMMARY: The primary treatment of malignant melanoma is a classical regimen of surgery combined with chemotherapy, targeted drugs, and immunotherapy. The purpose of this study was to explore the immune response mechanism of RNA binding protein RBM38 in the development of melanoma with the screening of effective immunodiagnostic models and targeted therapy. We found that RBM38, as an oncogene, promotes the proliferation, invasion, and migration of melanoma cells and is associated with immune infiltration and pathways. Our investigation presented the prognostic significance of RBM38-associated immune signature. In addition, this model may provide a potential strategy for improving the survival and immunotherapy of melanoma patients. ABSTRACT: Background: Current studies have revealed that RNA-binding protein RBM38 is closely related to tumor development, while its role in malignant melanoma remains unclear. Therefore, this research aimed to investigate the function of RBM38 in melanoma and the prognosis of the disease. Methods: Functional experiments (CCK-8 assay, cell colony formation, transwell cell migration/invasion experiment, wound healing assay, nude mouse tumor formation, and immunohistochemical analysis) were applied to evaluate the role of RBM38 in malignant melanoma. Immune-associated differentially expressed genes (DEGs) on RBM38 related immune pathways were comprehensively analyzed based on RNA sequencing results. Results: We found that high expression of RBM38 promoted melanoma cell proliferation, invasion, and migration, and RBM38 was associated with immune infiltration. Then, a five-gene (A2M, NAMPT, LIF, EBI3, and ERAP1) model of RBM38-associated immune DEGs was constructed and validated. Our signature showed superior prognosis capacity compared with other melanoma prognostic signatures. Moreover, the risk score of our signature was connected with the infiltration of immune cells, immune-regulatory proteins, and immunophenoscore in melanoma. Conclusions: We constructed an immune prognosis model using RBM38-related immune DEGs that may help evaluate melanoma patient prognosis and immunotherapy modalities.