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.
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