Unraveling the Relevance of ARL GTPases in Cutaneous Melanoma Prognosis Through Integrated Bioinformatics Analysis

Cutaneous melanoma (CM) is the deadliest skin cancer, whose molecular pathways underlying its malignancy remain unclear. Therefore, new information to guide evidence-based clinical decisions is required. Adenosine diphosphate (ADP)-ribosylation factor-like (ARL) proteins are membrane trafficking regulators whose biological relevance in CM is undetermined. Here, we investigated expression and its impact on CM prognosis and immune microenvironment through integrated bioinformatics analysis. Our study found that all 22 are differentially expressed in CM. Specifically, and are upregulated and is downregulated regardless of mutational frequency or copy number variations. According to TCGA data, and represent independent prognostic factors in CM as well as based on GEPIA and OncoLnc. To investigate the mechanisms by which and increase patient survival while reduces it, we evaluated their correlation with the immune microenvironment. CD4 T cells and neutrophil infiltrates are significantly increased by expression. Furthermore, expression was correlated with 17 out of 21 immune infiltrates, including CD8 T cells and M2 macrophages, described as having anti-tumoral activity. Likewise, ARL11 is interconnected with ZAP70, ADAM17, and P2RX7, which are implicated in immune cell activation. Collectively, this study provides the first evidence that , , and may influence CM progression, prognosis, and immune microenvironment remodeling.