Cuprotosis clusters predict prognosis and immunotherapy response in low-grade glioma

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Apoptosis Pub Date : 2023-09-15 DOI:10.1007/s10495-023-01880-y

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

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Abstract

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.

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杯状核团可预测低级别胶质瘤的预后和免疫疗法反应。

杯状细胞凋亡是一种新兴的细胞死亡模式，最近引起了全球研究人员的关注。然而，它对低级别胶质瘤（LGG）患者的影响尚未得到充分探讨。为了深入了解杯状细胞凋亡与 LGG 患者预后之间的关系，我们进行了这项研究，根据 18 个杯状细胞凋亡相关基因的表达将 LGG 患者分为两组。我们发现，A 组 LGG 患者的预后优于 B 组。此外，我们还确定了两个群组之间的差异表达基因（DEGs），并在TCGA训练队列中通过最小绝对收缩和选择算子（LASSO）分析建立了杯状红细胞增多症相关预后特征。该特征将LGG患者分为高危和低危组，其中高危组的总生存期（OS）明显短于低危组。TCGA内部验证队列、CGGA325队列和CGGA693队列证实了该特征对LGG患者预后的预测可靠性。此外，还利用提名图预测了每位患者的 1 年、3 年和 5 年 OS 率。对免疫检查点和肿瘤突变负荷（TMB）的分析表明，属于高危人群的患者从免疫疗法中获益的几率更大。功能实验证实，干扰特征基因 TNFRSF11B 可抑制 LGG 细胞的增殖和迁移。总之，这项研究揭示了杯状细胞增多症在LGG患者预后中的重要性。杯状红细胞增多症相关预后特征是预测患者预后和免疫治疗反应的可靠指标，有助于开发治疗LGG的新疗法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Apoptosis 生物-生化与分子生物学

CiteScore

9.10

自引率

4.20%

发文量

审稿时长

1 months

期刊介绍： Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.