{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T11:03:12Z","timestamp":1777028592408,"version":"3.51.4"},"reference-count":86,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["IP-2022-10-8720"],"award-info":[{"award-number":["IP-2022-10-8720"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institutional Grant of the University of Zadar, Croatia","award":["2023."],"award-info":[{"award-number":["2023."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Retinoblastoma (RB) and uveal melanoma (UM) remain vision-threatening and lethal ocular malignancies with limited molecular markers of differentiation state and prognosis. We investigated whether proteins governing endocytosis and signaling, including Megalin (LRP2), Cubilin (CUBN), Caveolin-1, GAIP-interacting protein C-terminus 1 (GIPC1), and Disabled homolog 2-interacting protein (DAB2IP), exhibit subtype-specific expression patterns in ocular tumors and whether these patterns are related to transcriptomic profiles and survival. Methods: Formalin-fixed, paraffin-embedded human ocular tissues included controls (n = 10), retinoblastoma (n = 10), and UM subtypes (epithelioid, spindle, mixoid; total n = 30). Immunofluorescence for LRP2, CUBN, CAV1, GIPC1, and DAB2IP was quantified using ImageJ (version 1.54g) across standardized high-power fields; per-specimen means were used for statistical analysis (Shapiro\u2013Wilk test; one-way ANOVA with Tukey\u2019s post hoc test). Public data analyses comprised: (i) overall survival in TCGA-UVM using GEPIA2; (ii) differential expression in GEO datasets (GSE62075: melanocytes vs. UM cell lines; GSE208143: retinoblastoma vs. pediatric control retina) and (iii) multivariate Cox proportional hazards regression analysis using the GEPIA3 online platform. Results: LRP2 expression was uniformly reduced across retinoblastoma and all UM subtypes versus control. CUBN expression decreased in retinoblastoma and epithelioid melanoma, was retained in spindle melanoma, and increased in mixoid-cell melanoma. CAV1 expression was increased in epithelioid melanoma but reduced in retinoblastoma, mixoid, and spindle melanomas. GIPC1 and DAB2IP expression were preserved in epithelioid melanoma yet significantly reduced in retinoblastoma and mixoid\/spindle melanomas. In TCGA-UVM, higher CAV1 and GIPC1 mRNA expression was associated with worse overall survival (p \u2248 0.025 and 0.036), whereas LRP2, CUBN, and DAB2IP expression were not significant. GEO analyses revealed no significant differences for the five genes in UM cell lines versus melanocytes (GSE62075). However, in retinoblastoma (GSE208143), LRP2 was downregulated, while CUBN, CAV1, GIPC1, and DAB2IP were upregulated. Conclusions: Endocytic\/signaling proteins exhibit distinct, subtype-linked expression in ocular tumors. Integration with public datasets highlights CAV1 and GIPC1 as adverse survival correlates in UM and positions LRP2\/CUBN\/DAB2IP dysregulation as features of ocular tumor biology, nominating candidate biomarkers and mechanistic targets.<\/jats:p>","DOI":"10.3390\/cancers17233785","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:56:34Z","timestamp":1764165394000},"page":"3785","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Linking Megalin, Cubilin, Caveolin-1, GIPC1 and Dab2IP Expression to Ocular Tumorigenesis: Profiles in Retinoblastoma, Choroidal Melanoma, and the Normal Human Eye"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5449-3427","authenticated-orcid":false,"given":"Petra","family":"Kova\u010devi\u0107","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospital Center of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6953-0135","authenticated-orcid":false,"given":"Petar","family":"Todorovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"},{"name":"Center for Translational Research in Biomedicine, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6529-5474","authenticated-orcid":false,"given":"Nela","family":"Kelam","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"},{"name":"Center for Translational Research in Biomedicine, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3979-6790","authenticated-orcid":false,"given":"Suzana","family":"Konjevoda","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, General Hospital Zadar, 23000 Zadar, Croatia"},{"name":"Department of Health Studies, University of Zadar, 23000 Zadar, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nenad","family":"Kunac","sequence":"additional","affiliation":[{"name":"Department of Pathology, Forensic Medicine and Cytology, University Hospital Centre Split, Spin\u010di\u0107eva 1, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josipa","family":"Marin Lovri\u0107","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Centre Split, Spin\u010di\u0107eva 1, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2182-2890","authenticated-orcid":false,"given":"Katarina","family":"Vukojevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"},{"name":"Center for Translational Research in Biomedicine, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"},{"name":"Department of Anatomy, School of Medicine, University of Mostar, 88000 Mostar, Bosnia and Herzegovina"},{"name":"Mediterranean Institute for Life Sciences (MedILS), University of Split, Me\u0161trovi\u0107evo \u0160etali\u0161te 45, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/eye.2016.275","article-title":"Uveal melanoma: Relatively rare but deadly cancer","volume":"31","author":"Kaliki","year":"2017","journal-title":"Eye"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/S0140-6736(11)61137-9","article-title":"Retinoblastoma","volume":"379","author":"Dimaras","year":"2012","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15021","DOI":"10.1038\/nrdp.2015.21","article-title":"Retinoblastoma","volume":"1","author":"Dimaras","year":"2015","journal-title":"Nat. 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