Cuprotosis Clusters Predicts Prognosis and Immunotherapy Response in Low-grade glioma

Abstract

Abstract Cuprotosis, a new cell death mode, has recently received increasing attention. However, the role of cuprotosis in low-grade glioma (LGG) remains unclear. In this study, we explored the relationship of cuprotosis with LGG patient prognosis and immune status. We divided LGG patients into cuprotosis clusters A and B based on the expression of 18 cuprotosis genes in LGG patients. The prognosis of patients in cuprotosis cluster A was better than cuprotosis cluster B. Cuprotosis clusters showed different immune cell infiltration and biological functions. We screened the differentially expressed genes (DEGs) between the different cuprotosis clusters and identified 6 DEGs (TNFRSF11B, METTL7B, SSTR2, OXTR, CDKN2C, and H19) to construct a cuprotosis-related prognostic signature to predict the prognosis of LGG patients through univariate cox-lasso-multivariate cox regression analysis. The signature split LGG patients into two risk groups. High-risk group showed significantly shorter overall survival (OS) time than low-risk group in the training group, internal and external validation groups. The nomogram further precisely predicted patients' 1, 3 and 5-year OS. The Sankey diagram visually displayed the correspondence of different clusters with risk scores and survival status. Similarly, we also found the relationship of tumor microenvironment (TME) infiltration and tumor mutation burden (TMB) with risk scores, and the high-risk group might benefit more from immunotherapy. In conclusion, our study highlighted the significant role of cuprotosis in LGG prognosis and TME infiltration. The cuprotosis-related prognostic signature would help us predict the prognosis of LGG patients and understand the LGG immune infiltration characterization, providing potential molecules for further molecularly targeted therapies and immunotherapeutic interventions in LGG.