ABSTRACT Background: The importance of BAG2 in malignancy is gradually being recognized, however, information on its role in uveal melanoma (UVM) is limited. We aimed to elucidate its function and potential mechanism of action in UVM. Methods: Using The Cancer Genome Atlas (TCGA) and GEO-related datasets, we analyzed the differential expression of BAG2 in tumors, combined with clinical information and methylation data to analyze the prognostic value of C15orf48, differential methylation and its association with UVM metastasis. In addition, correlation analysis explored the immunological characteristics of BAG2 in UVM and the response to immunotherapy. Finally, a prognostic model of ferroptosis-related genes was constructed and validated. Results: BAG2 is significantly downregulated in multiple cancers including UVM. Prognostic analysis showed that BAG2 was an independent prognostic factor for UVM. Abnormal methylation of BAG2 may affect the metastasis of UVM and be significantly associated with poor prognosis. Immune analysis clarified that BAG2 was significantly associated with UVM immune cell infiltration and multiple immune checkpoints, and low expression of BAG2 was more beneficial in immunotherapy. In addition, the prognostic model of ferroptosis we constructed has good performance in predicting overall survival and metastasis-free survival of UVM. Conclusions: BAG2 is an independent prognostic factor for UVM and may be a potential immune checkpoint for UVM.

中文翻译：

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BAG2是葡萄膜黑色素瘤的一种新型预后生物标志物和有前途的免疫治疗靶点

摘要背景：BAG2 在恶性肿瘤中的重要性逐渐被认识到，然而，有关其在葡萄膜黑色素瘤 (UVM) 中的作用的信息有限。我们的目的是阐明其在 UVM 中的功能和潜在作用机制。方法：利用癌症基因组图谱（TCGA）和GEO相关数据集，分析肿瘤中BAG2的差异表达，结合临床信息和甲基化数据分析C15orf48、差异甲基化及其与UVM转移的关系的预后价值。此外，相关分析探讨了UVM中BAG2的免疫学特征以及对免疫治疗的反应。最后，构建并验证了铁死亡相关基因的预后模型。结果：BAG2 在包括 UVM 在内的多种癌症中显着下调。预后分析显示BAG2是UVM的独立预后因素。BAG2异常甲基化可能影响UVM的转移并与不良预后显着相关。免疫分析阐明，BAG2与UVM免疫细胞浸润和多个免疫检查点显着相关，BAG2低表达更有利于免疫治疗。此外，我们构建的铁死亡预后模型在预测UVM的总生存率和无转移生存率方面具有良好的性能。结论：BAG2是UVM的独立预后因素，并且可能是UVM的潜在免疫检查点。