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

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.

Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy

“…FDX1 is a newly discovered gene that regulates cuprotosis [ 84–86 ]. Cuprotosis, a mode of programmed cell death, was recently recognized by TODD R. GOLUB’s team in 2022 and occurs through the direct combination of copper with lipid-acylated components of the TCA cycle, resulting in the clustering of lipid-acylated proteins and reduction of iron–sulfur cluster proteins, thereby leading to proteotoxic stress and ultimately cell death [ 87 , 88 ]. The effect of FDX1 expression on various diseases, such as clear cell carcinoma, colon adenocarcinoma, and polycystic ovary syndrome, has aroused broad concern [ 84 , 85 , 89 , 90 ].…”

Cuproptosis in glioblastoma: unveiling a novel prognostic model and therapeutic potential

“…Our CP-model indicated an inextricable link between copper-dependent cell death and tumor immune responses in glioblastoma when seen as a whole ( 40 ). Moreover, we have extended our analysis to include recent findings by Zhu et al., which highlight the prognostic significance of cuproptosis clusters in low-grade glioma (LGG) and their correlation with immunotherapy response ( 41 ). This study’s approach to categorizing patients based on cuproptosis-related DEGs mirrors our methodological framework in glioblastoma, underscoring the potential universality of cuproptosis as a prognostic marker across glioma subtypes.…”

Comprehending the cuproptosis and cancer-immunity cycle network: delving into the immune landscape and its predictive role in breast cancer immunotherapy responses and clinical endpoints

“…However, the excessive accumulation or anomalous distribution of copper can potentially trigger cuproptosis, a process of paramount significance for cellular viability. Scientific investigations have elucidated the close association between cuproptosis and the onset and progression of tumors, as copper assumes a pivotal role in governing tumor cell proliferation, invasiveness, and drug resistance (11). Furthermore, cuproptosis is intricately linked to the functioning of the immune system, given copper's vital contributions to immune cell activity and antioxidant defense (12).…”