Table1_A cuproptosis-related lncRNAs signature for prognosis, chemotherapy, and immune checkpoint blockade therapy of low-grade glioma.DOCX

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.

铜死亡（Cuproptosis）是一种新型细胞死亡方式，与三羧酸循环的线粒体呼吸过程密切相关。既往研究证实，长链非编码RNA（long non-coding RNAs, lncRNAs）可调控低级胶质瘤（low-grade glioma, LGG）的进展，但铜死亡相关长链非编码RNA（Cuproptosis-related lncRNAs, CRLs）在LGG中的潜在应用价值尚未得到系统探索。本研究针对癌症基因组图谱（The Cancer Genome Atlas, TCGA）与中国胶质瘤基因组图谱（Chinese Glioma Genome Atlas, CGGA）两个队列开展了全面的整合分析。研究首先基于预后相关CRLs，通过共识聚类算法筛选出两种不同的铜死亡亚型。为实现LGG的个体化生存预测，本研究在TCGA数据集中构建了一项包含CRNDE、HAR1A及FAM181A-AS1的预后特征模型。该预后特征模型展现出优异的预测性能与可靠性，并在CGGA_325与CGGA_693两个独立数据集中得到了验证。值得注意的是，高风险组患者的免疫细胞浸润水平与免疫检查点表达量均显著升高，提示该亚组患者或可从免疫检查点阻断（immune checkpoint blockade, ICB）治疗中获得更大获益。此外，该预后特征模型还筛选出了对化疗及ICB治疗敏感的患者群体。综上，本研究首次系统探索了CRLs在LGG发生发展中的作用机制，可为LGG的化疗与ICB治疗提供新的理论参考与研究思路。