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一种用于低级别胶质瘤预后、化疗及免疫检查点阻断治疗的铜死亡相关长链非编码RNA特征

A cuproptosis-related lncRNAs signature for prognosis, chemotherapy, and immune checkpoint blockade therapy of low-grade glioma.

作者信息

Yan Xiuwei, Wang Nan, Dong Jiawei, Wang Fang, Zhang Jiheng, Hu Xueyan, Zhao Hongtao, Gao Xin, Liu Zhihui, Li Yongzhe, Hu Shaoshan

机构信息

Department of Neurosurgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.

Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Front Mol Biosci. 2022 Aug 17;9:966843. doi: 10.3389/fmolb.2022.966843. eCollection 2022.

Abstract

Cuproptosis is a new type of cell death that is associated with mitochondrial respiration of the tricarboxylic acid cycle. Previous studies showed that long non-coding RNAs (lncRNAs) regulated low-grade glioma (LGG) progression. However, the potential applications of cuproptosis-related lncRNAs (CRLs) in LGG were not explored. A comprehensive analysis was performed in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) cohorts. We first screened two distinct cuproptosis subtypes based on prognostic CRLs using consensus clustering. To facilitate individualized survival prediction in LGG, we constructed a prognostic signature (including CRNDE, HAR1A, and FAM181A-AS1) in the TCGA dataset. The prognostic signature exhibited excellent predictive ability and reliability, which was validated in the CGGA_325 and CGGA_693 datasets. Notably, patients in the high-risk group had increased immune cell infiltration and expression of immune checkpoints, which indicated that they may benefit more from immune checkpoint blockade (ICB) therapy. Finally, the prognostic signature screened the population with sensitivity to chemotherapy and ICB therapy. In summary, this study initially explored the mechanism of CRLs in LGG and provides some insights into chemotherapy and ICB therapy of LGG.

摘要

铜死亡是一种新型的细胞死亡方式,与三羧酸循环的线粒体呼吸相关。先前的研究表明,长链非编码RNA(lncRNAs)调节低级别胶质瘤(LGG)的进展。然而,与铜死亡相关的lncRNAs(CRLs)在LGG中的潜在应用尚未得到探索。我们在癌症基因组图谱(TCGA)和中国胶质瘤基因组图谱(CGGA)队列中进行了全面分析。我们首先使用一致性聚类基于预后CRLs筛选出两种不同的铜死亡亚型。为了便于对LGG进行个体化生存预测,我们在TCGA数据集中构建了一个预后特征(包括CRNDE、HAR1A和FAM181A-AS1)。该预后特征表现出优异的预测能力和可靠性,并在CGGA_325和CGGA_693数据集中得到验证。值得注意的是,高风险组患者的免疫细胞浸润和免疫检查点表达增加,这表明他们可能从免疫检查点阻断(ICB)治疗中获益更多。最后,该预后特征筛选出了对化疗和ICB治疗敏感的人群。总之,本研究初步探索了CRLs在LGG中的机制,并为LGG的化疗和ICB治疗提供了一些见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ab4/9428515/cda8ed779ff1/fmolb-09-966843-g001.jpg

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