{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:13:40Z","timestamp":1760235220393,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,7]],"date-time":"2021-08-07T00:00:00Z","timestamp":1628294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Uveal melanoma (UM) metastasize haematogeneously, and tumor blood vessel density is an important prognostic factor. We hypothesized that proangiogenic factors such as angiopoietin-1 (ANG-1) and angiopoietin-2 (ANG-2), two targetable cytokines, might play a role in tumor development and metastatic behavior. mRNA levels of ANG-1 and ANG-2 were determined in 64 tumors using an Illumina HT-12 v4 mRNA chip and compared to clinical, pathologic, and genetic tumor parameters. Tissue expression was also determined by immunohistochemistry (IHC). Samples of aqueous humor were collected from 83 UM-containing enucleated eyes and protein levels that were determined in a multiplex proximity extension assay. High tissue gene expression of ANG-2, but not of ANG-1, was associated with high tumor thickness, high largest basal diameter, involvement of the ciliary body, and with UM-related death (ANG-2 mRNA p &lt; 0.001; ANG-2 aqueous protein p &lt; 0.001). The presence of the ANG-2 protein in aqueous humor correlated with its mRNA expression in the tumor (r = 0.309, p = 0.03). IHC showed that ANG-2 was expressed in macrophages as well as tumor cells. The presence of ANG-2 in the tumor and in aqueous humor, especially in high-risk tumors, make ANG-2 a potential targetable cytokine in uveal melanoma.<\/jats:p>","DOI":"10.3390\/cancers13163986","type":"journal-article","created":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T21:49:41Z","timestamp":1628459381000},"page":"3986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["In Uveal Melanoma, Angiopoietin-2 but Not Angiopoietin-1 Is Increased in High-Risk Tumors, Providing a Potential Druggable Target"],"prefix":"10.3390","volume":"13","author":[{"given":"Anna M.W.","family":"ten Voorde","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3537-3662","authenticated-orcid":false,"given":"Annemijn P.A.","family":"Wierenga","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rogier J.","family":"Nell","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter A.","family":"van der Velden","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregorius P.M.","family":"Luyten","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1437-214X","authenticated-orcid":false,"given":"Robert M.","family":"Verdijk","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Department of Pathology, Section Ophthalmic Pathology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2261-3820","authenticated-orcid":false,"given":"Martine J.","family":"Jager","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/j.ophtha.2011.01.040","article-title":"Uveal melanoma: Trends in incidence, treatment, and survival","volume":"118","author":"Singh","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1001\/archopht.123.12.1639","article-title":"Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26","volume":"123","author":"Reynolds","year":"2005","journal-title":"Arch. 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