Integrative analysis of the cuproptosis-related gene ATP7B in the prognosis and immune infiltration of IDH1 wild-type glioma.

ABSTRACT

Glioma is the most common malignant tumor in the brain and the central nervous system with a poor prognosis, and wild-type isocitrate dehydrogenase (IDH) glioma indicates a worse prognosis. Cuproptosis is a recently discovered form of cell death regulated by copper-dependent mitochondrial respiration. However, the effect of cuproptosis on tumor prognosis and immune infiltration is not clear. In this research, we analyzed of public databases to show the correlation between cuproptosis-related genes and the prognosis of IDH1 wild-type glioma. Nine out of 12 genes were upregulated in IDH1 wild-type glioma patients, and 6 genes were significantly associated with overall survival (OS), while 5 genes were associated with progression-free survival (PFS). Then, we constructed a prognostic cuproptosis-related gene signature for IDH1 wild-type glioma patients. ATP7B was considered an independent prognostic indicator, and a low expression level of ATP7B was related to a shorter period of OS and PFS. Moreover, downregulation of ATP7B was correlated not only with the infiltration of activated NK cells, CD8 + T cells and M2 macrophages; but also with high expression of immune checkpoint genes and tumor mutation burden (TMB). In the IDH1 wild-type glioma tissues we collected, our data also confirmed that high tumor grade was accompanied by low expression of ATP7B and high expression of PD-L1, which was associated with increasing infiltration of CD8 + immune cells. In conclusion, our research constructed a prognostic cuproptosis-related gene signature model to predict the prognosis of IDH1 wild-type glioma. ATP7B is deemed to be a potential prognostic indicator and novel immunotherapy biomarker for IDH1 wild-type glioma patients.