{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:26:07Z","timestamp":1771921567804,"version":"3.50.1"},"reference-count":76,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"iNOVA4Health","award":["UIDB\/04462\/2020"],"award-info":[{"award-number":["UIDB\/04462\/2020"]}]},{"name":"Liga Portuguesa Contra o Cancro \u2013 N\u00facleo Regional do Sul","award":["LPCC-NRS"],"award-info":[{"award-number":["LPCC-NRS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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+ 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+ 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.<\/jats:p>","DOI":"10.3390\/ijms22179260","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T09:53:23Z","timestamp":1630058003000},"page":"9260","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Unraveling the Relevance of ARL GTPases in Cutaneous Melanoma Prognosis through Integrated Bioinformatics Analysis"],"prefix":"10.3390","volume":"22","author":[{"given":"Cheila","family":"Brito","sequence":"first","affiliation":[{"name":"Unidade de Investiga\u00e7\u00e3o em Patobiologia Molecular (UIPM) do Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5932-6211","authenticated-orcid":false,"given":"Bruno","family":"Costa-Silva","sequence":"additional","affiliation":[{"name":"Champalimaud Research, Champalimaud Centre for the Unknown, Avenida de Bras\u00edlia, 1400-038 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8867-2407","authenticated-orcid":false,"given":"Duarte C.","family":"Barral","sequence":"additional","affiliation":[{"name":"iNOVA4Health, CEDOC, NOVA Medical School, NMS, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}]},{"given":"Marta","family":"Pojo","sequence":"additional","affiliation":[{"name":"Unidade de Investiga\u00e7\u00e3o em Patobiologia Molecular (UIPM) do Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"ref_1","first-page":"210","article-title":"Update in Genetic Susceptibility in Melanoma","volume":"3","author":"Potrony","year":"2015","journal-title":"J. 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