Mejía-García Alejandro, Orozco Carlos A, Herzog Julius, Alarcón-Betancourth Oscar, Meneses-Torres Alexandra, Ramírez Marcela, González Johanna, Zambrano Yina, Combita Alba Lucia, Bonilla Diego A, Frietze Seth
Department of Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada.
Cancer Biology Research Group, Instituto Nacional de Cancerología, Bogotá 110311, Colombia.
Int J Mol Sci. 2025 May 1;26(9):4317. doi: 10.3390/ijms26094317.
Uveal melanoma (UVM) is an aggressive cancer with a poor prognosis, particularly in metastatic cases. This study aimed to develop and validate a novel extracellular matrix (ECM) gene expression signature to predict prognosis and stratify patients by risk. ECM-related genes were identified and used to construct a prognostic model through Lasso-Cox regression analysis, leveraging RNA sequencing data from 80 UVM patients in The Cancer Genome Atlas (TCGA). The model was validated using an independent cohort of 63 UVM patients. Survival analyses, immune infiltration profiling, and functional enrichment analyses were conducted to evaluate the biological significance and clinical utility of the signature. The ECM signature stratified patients into high- and low-risk groups with significant differences in survival outcomes. High-risk patients showed elevated expression of and , which are associated with ECM remodeling and immune modulation, alongside increased infiltration of immunosuppressive cells, such as M2 macrophages. Validation confirmed the prognostic value of the signature across cohorts. Functional analyses highlighted the involvement of ECM-related pathways, epithelial-mesenchymal transition, and immune system interactions in tumor progression. This ECM gene expression signature is a robust prognostic tool for UVM, offering insights into tumor biology and immune microenvironment interactions. It holds promise for improving patient stratification and guiding personalized therapeutic strategies. Further research is warranted to explore the functional roles of these genes in UVM progression.
葡萄膜黑色素瘤（UVM）是一种侵袭性癌症，预后较差，尤其是在转移性病例中。本研究旨在开发并验证一种新的细胞外基质（ECM）基因表达特征，以预测预后并按风险对患者进行分层。通过套索-考克斯回归分析，利用来自癌症基因组图谱（TCGA）中80例UVM患者的RNA测序数据，鉴定出ECM相关基因并用于构建预后模型。该模型在一个由63例UVM患者组成的独立队列中进行了验证。进行生存分析、免疫浸润分析和功能富集分析，以评估该特征的生物学意义和临床实用性。ECM特征将患者分为高风险和低风险组，生存结果存在显著差异。高风险患者显示出与ECM重塑和免疫调节相关的 和 的表达升高，同时免疫抑制细胞如M2巨噬细胞的浸润增加。验证证实了该特征在不同队列中的预后价值。功能分析突出了ECM相关通路、上皮-间质转化和免疫系统相互作用在肿瘤进展中的作用。这种ECM基因表达特征是一种用于UVM的强大预后工具，为肿瘤生物学和免疫微环境相互作用提供了见解。它有望改善患者分层并指导个性化治疗策略。有必要进一步研究以探索这些基因在UVM进展中的功能作用。
