铜剂诱导细胞死亡(cuprotosis)聚集在低级别胶质瘤中可预测预后和免疫治疗反应。
Cuprotosis clusters predict prognosis and immunotherapy response in low-grade glioma.
发表日期:2023 Sep 15
作者:
Wenjun Zhu, Ziqi Chen, Min Fu, Qianxia Li, Xin Chen, Xiaoyu Li, Na Luo, Wenhua Tang, Feng Yang, Yiling Zhang, Yuanyuan Zhang, Xiaohong Peng, Guangyuan Hu
来源:
Genes & Diseases
摘要:
铜病毒病是一种新兴的细胞死亡方式,近年来引起了全球研究者的关注。然而,它对低级别胶质瘤(LGG)患者的影响尚未完全探索。为了更深入地了解铜病毒病与LGG患者预后之间的关系,我们进行了这项研究,将LGG患者根据18个与铜病毒病相关的基因的表达分成两个簇。我们发现,A簇的LGG患者预后较B簇的患者要好。这两个簇在免疫细胞浸润和生物学功能方面也存在差异。此外,我们在TCGA训练队列中鉴定了两个簇之间的差异表达基因(DEGs),并通过最小绝对收缩和选择算子(LASSO)分析开发了一个与铜病毒病相关的预后标志。这个标志将LGG患者分为高风险和低风险组,高风险组的整体生存时间明显短于低风险组。TCGA内部验证队列、CGGA325队列和CGGA693队列的结果证实了该标志在LGG患者预后预测方面的可靠性。此外,我们利用一种演算图来预测每个患者的1年、3年和5年总生存率。免疫检查点和肿瘤突变负荷(TMB)的分析表明,高风险组的个体更有可能从免疫治疗中获益。功能实验证实,干预标志基因TNFRSF11B可以抑制LGG细胞的增殖和迁移。总的来说,本研究揭示了铜病毒病在LGG患者预后中的重要性。与铜病毒病相关的预后标志是预测患者预后和免疫治疗反应的可靠指标,并有助于开发LGG的新疗法。© 2023. 作者。
Cuprotosis, an emerging mode of cell death, has recently caught the attention of researchers worldwide. However, its impact on low-grade glioma (LGG) patients has not been fully explored. To gain a deeper insight into the relationship between cuprotosis and LGG patients' prognosis, we conducted this study in which LGG patients were divided into two clusters based on the expression of 18 cuprotosis-related genes. We found that LGG patients in cluster A had better prognosis than those in cluster B. The two clusters also differed in terms of immune cell infiltration and biological functions. Moreover, we identified differentially expressed genes (DEGs) between the two clusters and developed a cuprotosis-related prognostic signature through the least absolute shrinkage and selection operator (LASSO) analysis in the TCGA training cohort. This signature divided LGG patients into high- and low-risk groups, with the high-risk group having significantly shorter overall survival (OS) time than the low-risk group. Its predictive reliability for prognosis in LGG patients was confirmed by the TCGA internal validation cohort, CGGA325 cohort and CGGA693 cohort. Additionally, a nomogram was used to predict the 1-, 3-, and 5-year OS rates of each patient. The analysis of immune checkpoints and tumor mutation burden (TMB) has revealed that individuals belonging to high-risk groups have a greater chance of benefiting from immunotherapy. Functional experiments confirmed that interfering with the signature gene TNFRSF11B inhibited LGG cell proliferation and migration. Overall, this study shed light on the importance of cuprotosis in LGG patient prognosis. The cuprotosis-related prognostic signature is a reliable predictor for patient outcomes and immunotherapeutic response and can help to develop new therapies for LGG.© 2023. The Author(s).