Abstract

BackgroundThe existing studies indicate that RNA binding proteins (RBPs) are closely correlated with the genesis and development of cancers. However, the role of RBPs in cutaneous melanoma remains largely unknown. Therefore, the present study aims to establish a reliable prognostic signature based on RBPs to distinguish cutaneous melanoma patients with different prognoses and investigate the immune infiltration of patients.MethodsAfter screening RBPs from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, Cox and least absolute shrinkage and selection operator (LASSO) regression analysis were then used to establish a prediction model. The relationship between the signature and the abundance of immune cell types, the tumor microenvironment (TME), immune-related pathways, and immune checkpoints were also analyzed.ResultsIn total, 7 RBPs were selected to establish the prognostic signature. Patients categorized as a high-risk group demonstrated worse overall survival (OS) rates compared to those of patients categorized as a low-risk group. The signature was validated in an independent external cohort and indicated a promising prognostic ability. Further analysis indicated that the signature wasan independent prognostic indicator in cutaneous melanoma. A nomogram combining risk score and clinicopathological features was then established to evaluate the 3- and 5-year OS in cutaneous melanoma patients. Analyses of immune infiltrating, the TME, immune checkpoint, and drug susceptibility revealed significant differences between the two groups. GSEA analysis revealed that basal cell carcinoma, notch signaling pathway, melanogenesis pathways were enriched in the high-risk group, resulting in poor OS.ConclusionWe established and validated a robust 7-RBP signature that could be a potential biomarker to predict the prognosis and immunotherapy response of cutaneous melanoma patients, which provides new insights into cutaneous melanoma immunotherapeutic strategies.

Highlights

  • Cutaneous melanoma is the most aggressive and dangerous skin malignancy with high levels of morbidity, and its incidence continues to increase each year (Swetter et al, 2019)

  • Gene Set Enrichment Analysis (GSEA) analysis revealed that basal cell carcinoma, notch signaling pathway, melanogenesis pathways were enriched in the high-risk group, resulting in poor overall survival (OS)

  • A systematic analysis was carried out for the critical roles and the potential prognostic values of RNA binding proteins (RBPs) played in cutaneous melanoma

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Summary

Introduction

Cutaneous melanoma is the most aggressive and dangerous skin malignancy with high levels of morbidity, and its incidence continues to increase each year (Swetter et al, 2019). Due to the phenotype and genetic heterogeneity of malignant melanoma, conventional clinicopathological features are still limited or restricted in their ability to accurately predict individual outcomes (Diamantopoulos and Gogas, 2016). These sobering data highlight the urgent need for the development of novel malignant melanoma-specific genomic models to accurately predict clinical outcomes of melanoma patients and provide a guide to more effective individual therapies. The present study aims to establish a reliable prognostic signature based on RBPs to distinguish cutaneous melanoma patients with different prognoses and investigate the immune infiltration of patients

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