RAB37 Exerts a Context-Dependent Role in Cutaneous Melanoma Progression by Promoting Tumor Cell Proliferation and Being Associated with Favorable Immune Characteristics

Abstract

Background Rab proteins and small GTPase-mediated vesicle trafficking pathways play important roles in tumor progression and the tumor microenvironment. However, the biological function and clinical significance of RAB37 in cutaneous melanoma (CM) remain unclear. This study investigated the expression pattern, prognostic value, biological function, and immune-related characteristics of RAB37 in CM. Methods RAB37 expression and prognostic significance were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Kaplan–Meier and Cox regression analyses were performed to evaluate prognostic value. Spearman correlation analysis assessed associations between RAB37 expression and immune cell infiltration, immune checkpoint blockade (ICB)-related signatures, and inflammatory cytokines. Functional roles of RAB37 were validated using loss- and gain-of-function experiments in A375 and WM-115 melanoma cells. CCK-8, EdU, and Transwell assays evaluated cell proliferation and migration. Single-cell functional analysis was performed using CancerSEA. Results RAB37 expression was significantly higher in metastatic than in primary CM tissues. Elevated RAB37 expression and hypermethylation of the cg26263675 CpG site were associated with favorable survival outcomes. A prognostic nomogram integrating clinicopathological characteristics and RAB37 methylation was established. Functional experiments demonstrated that RAB37 knockdown significantly inhibited, whereas RAB37 overexpression promoted, melanoma cell proliferation and migration in both A375 and WM-115 cells. RAB37 expression was significantly associated with immune cell infiltration, ICB-related signatures, inflammatory cytokines, and immune-related pathways, including T-cell receptor signaling, PD-1 checkpoint signaling, IL-2/STAT5 signaling, and inflammatory responses. Single-cell analysis further revealed a positive association between RAB37 expression and inflammation-related functional states. Conclusion RAB37 exhibits a context-dependent role in CM by promoting malignant cellular behaviors while being associated with immune-related characteristics and favorable clinical outcomes. These findings suggest that RAB37 may serve as a potential prognostic biomarker and provide new insights into the interplay between CM progression and the tumor immune microenvironment.