Tao Yulin, Peng Yirui, Zhu Haibo, Xiong Minqi, Zhou Qiong, Ouyang Jun
Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, P. R. China.
Department of Ophthalmology, Jiujiang No. 1 People's Hospital, Jiujiang, Jiangxi Province, P. R. China.
Medicine (Baltimore). 2025 Jun 20;104(25):e42574. doi: 10.1097/MD.0000000000042574.
Uveal melanoma (UM) is a primary intraocular malignancy with a high-risk of metastasis. Currently, there are no studies that construct prognostic models based on immune-related molecular subtypes. We performed unsupervised clustering of immune cell infiltration matrices based on the the cancer genome atlas-uveal melanoma (TCGA-UVM) dataset, identifying 2 clusters with distinct expression patterns of immune checkpoint and immune activation related genes. gene ontology/Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that genes in the immune-related gene modules identified by WGCNA were associated with immune activity and cell proliferation. Using Cox and LASSO regression analysis based on the immune-related gene modules to construct a prognostic model. The prognostic model was validated in external datasets of Gene Expression Omnibus (GEO) database. We constructed a prognostic model comprising genes S100A4, KCNIP3, PARP8, ORAI2, MMP12, ISG20, MMP9, and CEBPB. The model stratified patients into high and low-risk groups, with the high-risk group showing poorer prognosis. The model's predictive accuracy was validated with the AUC values exceeding 0.8 for 1-year, 3-year, and 5-year survival rates and confirmed in external datasets GSE22138 and GSE84976. Differential gene analysis between risk groups highlighted the association with immune response and cell proliferation functions. The CEBPB gene in the model played crucial roles in tumor progression. In vivo and in vitro experiments validated the impact of CEBPB on the biological functions of UM. Experiments in UM cells revealed that CEBPB promoted cell proliferation, migration and invasion, as well as suppressing apoptosis, indicating its potential as a therapeutic target. The prognostic model based on 8 immune-related genes effectively predicted the survival outcomes of UM. Knockdown of CEBPB significantly reduced the progression of UM, suggesting that it could be a potential therapeutic target for UM.
葡萄膜黑色素瘤（UM）是一种具有高转移风险的原发性眼内恶性肿瘤。目前，尚无基于免疫相关分子亚型构建预后模型的研究。我们基于癌症基因组图谱 - 葡萄膜黑色素瘤（TCGA - UVM）数据集对免疫细胞浸润矩阵进行无监督聚类，确定了2个具有不同免疫检查点和免疫激活相关基因表达模式的簇。基因本体论/京都基因与基因组百科全书富集分析表明，加权基因共表达网络分析（WGCNA）确定的免疫相关基因模块中的基因与免疫活性和细胞增殖相关。使用基于免疫相关基因模块的Cox和LASSO回归分析构建预后模型。该预后模型在基因表达综合数据库（GEO）的外部数据集中得到验证。我们构建了一个包含S100A4、KCNIP3、PARP8、ORAI2、MMP12、ISG20、MMP9和CEBPB基因的预后模型。该模型将患者分为高风险组和低风险组，高风险组预后较差。该模型的预测准确性通过1年、3年和5年生存率的AUC值超过0.8得到验证，并在外部数据集GSE22138和GSE84976中得到证实。风险组之间的差异基因分析突出了与免疫反应和细胞增殖功能的关联。模型中的CEBPB基因在肿瘤进展中起关键作用。体内和体外实验验证了CEBPB对UM生物学功能的影响。对UM细胞的实验表明，CEBPB促进细胞增殖、迁移和侵袭，并抑制细胞凋亡，表明其作为治疗靶点的潜力。基于8个免疫相关基因的预后模型有效地预测了UM的生存结果。敲低CEBPB显著降低了UM的进展，表明它可能是UM的潜在治疗靶点。
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