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

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.

A novel prognostic signature of cuproptosis-related genes and the prognostic value of FDX1 in gliomas

“… Ouyang et al (2022) presented models based on lncRNA and CRG levels; cuproptosis-associated glutaminase gene expression reflected the prognosis of glioma patients. The prognostic model of Yan et al (2022) used the levels of cuproptosis-associated lncRNAs to identify appropriate immune checkpoint blockade (ICB) therapies for LGG patients. We employed LASSO Cox’s regression analysis when constructing our prognostic model; the risk score was based on the levels of five CRGs (FDX1, DLD, LIAS, LIPT1, and PDHA1).…”

Cuproptosis-related gene signature stratifies lower-grade glioma patients and predicts immune characteristics

“…Moreover, Chen et alestablished a cuproptosis activity score (CuAS) based on bulk tumor and single-cell transcriptome data, suggesting that cuproptosis mediates glioma aggressiveness and neoplasm-immune interactions ( Chen et al, 2022 ). In addition, Yan et alreported that cuproptosis-related lncRNAs can guide LGG treatment, as they could divide LGG patients into different groups according to the response to immunotherapy ( Yan et al, 2022 ). In addition, two subclusters of glioma patients were identified based on CRG expression, which was correlated with tumor driver gene mutations and the response to chemotherapy, according to Wang et al ( Wang et al, 2022 ).…”

Systematic Analysis of a Pyroptosis-Related Signature to Predict the Prognosis and Immune Microenvironment of Lower-Grade Glioma

“…This work constructed a novel prognostic model using a LASSO analysis, and it included six PRGs, namely CASP4, CASP5, CASP9, GSDMC, PLCG1, and IL18. Recent studies have shown that genes related to cuproptosis [ 32 , 33 ] and ferroptosis [ 34 , 35 ] are predictive of the prognosis of LGG patients, and corresponding prognostic models have been constructed. Compared with them, our model has good 1-, 3-, 5- year AUC values ( Supplementary Table S1 ).…”

“…The following supporting information can be downloaded at: , Figure S1: Cox proportional hazards (PH) test before constructing the nomogram; Table S1: Comparison of AUC values of different prognostic models based on TCGA-LGG data. References [ 32 , 33 , 34 , 35 ] are cited in Supplementary Materials…”