{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:21:29Z","timestamp":1784193689564,"version":"3.55.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Uveal melanoma (UM), arising from melanocytes in the choroid, accounts for 3% to 5% of all melanocytic tumors and over 70% of intraocular malignancies. Despite effective local treatments, metastasis remains a significant challenge, with more than half of patients developing metastatic disease within ten years. Conventional therapies often yield poor outcomes, highlighting the urgent need for novel therapeutic strategies to enhance survival and prognosis for UM patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a detailed analysis of the GSE139829 dataset, focusing on scRNA-seq data from eight primary UM patients and three with metastatic disease. Through clustering and marker gene expression analyses, we identified distinct subtypes of UM tumor cells and examined their transcriptional, metabolic, and intercellular communication profiles. We developed a novel prognostic model, PCOLCE TCs Risk Score (PTRS), centered on the C5 <jats:italic>PCOLC<\/jats:italic>E+ tumor cells, which was validated through <jats:italic>in vitro<\/jats:italic> functional assays. Additionally, we performed immune infiltration and metabolic pathway analyses to elucidate tumor-immune interactions and their clinical significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified eight distinct cell types in UM and classified tumor subpopulations into six subgroups. The C5 <jats:italic>PCOLCE<\/jats:italic>+ TCs subpopulation was highlighted as crucial in UM malignancy, demonstrating high differentiation potential and a significant role in tumor progression. CellChat analysis revealed substantial communication between C5 <jats:italic>PCOLCE<\/jats:italic>+ TCs and fibroblasts, suggesting their involvement in tumor growth and extracellular matrix remodeling. Metabolic pathway analysis indicated enhanced oxidative phosphorylation and glutathione metabolism in this subpopulation. Additionally, we developed a PTRS model based on C5 <jats:italic>PCOLCE<\/jats:italic>+ TCs, identifying <jats:italic>CITED1<\/jats:italic> as a high-risk gene that promotes UM cell proliferation, invasion, and migration <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study provides insights into UM metastasis via single-cell analysis, identifying C5 <jats:italic>PCOLCE<\/jats:italic>+ TCs as key malignancy drivers associated with oxidative phosphorylation and immune interactions. Our PTRS model highlights <jats:italic>CITED1<\/jats:italic> as a high-risk gene that promotes UM cell proliferation, paving the way for new prognostic models and therapeutic targets to enhance patient outcomes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1493752","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T06:33:13Z","timestamp":1732084393000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Single-cell RNA sequencing reveals key molecular drivers and immune landscape in uveal melanoma: implications for targeted therapy and prognostic modeling"],"prefix":"10.3389","volume":"15","author":[{"given":"Zeyu","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikai","family":"Xiahou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.95103s8251","article-title":"Overview of ultraviolet radiation and cancer: what is the link? 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