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BAG2是葡萄膜黑色素瘤中一种新型的预后生物标志物和有前景的免疫治疗靶点。

BAG2 Is a Novel Prognostic Biomarker and Promising Immunotherapy Target in Uveal Melanoma.

作者信息

Li Chaolin, Shi Hao

机构信息

Jinniu District Maternal and Child Health Hospital, Chengdu, China.

出版信息

Crit Rev Eukaryot Gene Expr. 2023;33(6):55-71. doi: 10.1615/CritRevEukaryotGeneExpr.2023048565.

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 BAG2, 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.

摘要

背景

BAG2在恶性肿瘤中的重要性正逐渐得到认可,然而,其在葡萄膜黑色素瘤(UVM)中的作用信息有限。我们旨在阐明其在UVM中的功能及潜在作用机制。

方法

利用癌症基因组图谱(TCGA)和GEO相关数据集,我们分析了BAG2在肿瘤中的差异表达,结合临床信息和甲基化数据来分析BAG2的预后价值、差异甲基化及其与UVM转移的关联。此外,相关性分析探讨了BAG2在UVM中的免疫特征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著下调。预后分析表明,BAG2是UVM的独立预后因素。BAG2的异常甲基化可能影响UVM的转移,并与不良预后显著相关。免疫分析表明,BAG2与UVM免疫细胞浸润和多个免疫检查点显著相关,BAG2低表达在免疫治疗中更具优势。此外,我们构建的铁死亡预后模型在预测UVM的总生存期和无转移生存期方面具有良好性能。

结论

BAG2是UVM的独立预后因素,可能是UVM的潜在免疫检查点。

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