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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1493752
This article is part of the Research Topic Integrating Molecular Mechanisms, Immunotherapy, and Drug Sensitivity in Cancer Immunology and Oncology View all 3 articles

Single-Cell RNA Sequencing Reveals Key Molecular Drivers and Immune Landscape in Uveal Melanoma: Implications for Targeted Therapy and Prognostic Modeling

Provisionally accepted
Zeyu Song Zeyu Song 1Wenwen Shao Wenwen Shao 2Zhikai Xiahou Zhikai Xiahou 3Yue Xu Yue Xu 1Xiaofeng Zhang Xiaofeng Zhang 1*
  • 1 Department of Ophthalmology, The Fourth Affiliated Hospital of Soochow University, Suzhou, China., Suzhou, China
  • 2 Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
  • 3 China Institute of Sport and Health Science, Beijing Sport University, Beijing, China

The final, formatted version of the article will be published soon.

    Background: 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. Methods: 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 PCOLCE+ tumor cells, which was validated through in vitro functional assays. Additionally, we performed immune infiltration and metabolic pathway analyses to elucidate tumor-immune interactions and their clinical significance. Results: We identified eight distinct cell types in uveal melanoma (UM) and classified tumor subpopulations into six subgroups. The C5 PCOLCE+ 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 PCOLCE+ 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 PCOLCE+ TCs, identifying CITED1 as a high-risk gene that promotes UM cell proliferation, invasion, and migration in vitro. Conclusion: This study provides insights into UM metastasis via single-cell analysis, identifying C5 PCOLCE+ TCs as key malignancy drivers associated with oxidative phosphorylation and immune interactions. Our PTRS model highlights CITED1 as a high-risk gene that promotes UM cell proliferation, paving the way for new prognostic models and therapeutic targets to enhance patient outcomes.

    Keywords: single-cell RNA sequencing, Uveal Melanoma, CITED1, Immune Cell Infiltration, Prognostic biomarkers

    Received: 09 Sep 2024; Accepted: 01 Nov 2024.

    Copyright: © 2024 Song, Shao, Xiahou, Xu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xiaofeng Zhang, Department of Ophthalmology, The Fourth Affiliated Hospital of Soochow University, Suzhou, China., Suzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.