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Unraveling the Relevance of ARL GTPases in Cutaneous Melanoma Prognosis through Integrated Bioinformatics Analysis.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Aug 26; Vol. 22 (17). Date of Electronic Publication: 2021 Aug 26. - Publication Year :
- 2021
-
Abstract
- 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 ARL expression and its impact on CM prognosis and immune microenvironment through integrated bioinformatics analysis. Our study found that all 22 ARLs are differentially expressed in CM. Specifically, ARL1 and ARL11 are upregulated and ARL15 is downregulated regardless of mutational frequency or copy number variations. According to TCGA data, ARL1 and ARL15 represent independent prognostic factors in CM as well as ARL11 based on GEPIA and OncoLnc. To investigate the mechanisms by which ARL1 and ARL11 increase patient survival while ARL15 reduces it, we evaluated their correlation with the immune microenvironment. CD4 <superscript>+</superscript> T cells and neutrophil infiltrates are significantly increased by ARL1 expression. Furthermore, ARL11 expression was correlated with 17 out of 21 immune infiltrates, including CD8 <superscript>+</superscript> 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 ARL1 , ARL11 , and ARL15 may influence CM progression, prognosis, and immune microenvironment remodeling.
- Subjects :
- Animals
Biomarkers, Tumor
Cell Communication
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Melanoma diagnosis
Melanoma mortality
Neoplasm Metastasis
Neoplasm Staging
Promoter Regions, Genetic
Skin Neoplasms diagnosis
Skin Neoplasms mortality
Transport Vesicles
Tumor Microenvironment genetics
Tumor Microenvironment immunology
Workflow
Melanoma, Cutaneous Malignant
ADP-Ribosylation Factors genetics
ADP-Ribosylation Factors metabolism
Computational Biology methods
Disease Susceptibility
Melanoma etiology
Melanoma metabolism
Membrane Proteins genetics
Membrane Proteins metabolism
Skin Neoplasms etiology
Skin Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34502169
- Full Text :
- https://doi.org/10.3390/ijms22179260