An advanced cuprotosis-related long non-coding RNA signature predicts the prognosis of hepatocellular carcinoma

Abstract

Cuprotosis was discovered as a previously unidentified mode of cell death in March 2022. However, the relationship between this novel copper-mediated cell death and non-coding RNA has not been explored in Hepatocellular carcinoma (HCC). We developed a useful predictive model based on the TCGA-LIHC using four cuprotosis-related lncRNAs (AC026401.3, NRAV, CAPN10-DT, and SNHG4). As determined by the Kaplan-Meier survival analysis, the median survival time of those in the high-risk group was significantly lower than that of those in the low-risk group (P＜0.001). The risk score (0.772) has a much greater area under the curve (AUC) than the stage (0.671), age (0.531), gender (0.509), or grade (0.499). We used CIBERSORT, QUNANTISEQ, XCELL, CIBERSORT-ABS, EPIC, TIMER, and single-sample gene set enrichment analysis (ssGSEA) to compare immune cell infiltration, immunological function, and immune checkpoint related gene expression. And ssGSEA analysis revealed that the expression of 12 types of immune function genes differed between high- and low-risk groups. In the high-risk group, the expression of genes involved in APC-co-stimulation, checkpoint, human leukocyte antigen (HLA), MHC class I, T cell-co-stimulation, and so on were significantly up-regulated, whereas type I IFN response and type II IFN response were markedly down-regulated. CD274, HAVCR2, CTLA4, VTCN1, CD27, and CD200RL expression levels were all greater in the high-risk group than in the low-risk group, with the exception of ADORA2A. To sum up, the model based on the signature of 4 kinds of cuprotosis-related lncRNAs can effectively assess the prognosis and survival of HCC patients.