Construction and Validation of a Novel Cuproptosis-associated lncRNA Signature as a Prognostic Biomarker in Hepatocellular Carcinoma

Abstract

Background Hepatocellular carcinoma (HCC) has been found as a highly lethal malignancy worldwide that has an extremely unfavorable prognosis. A considerable number of long non-coding RNAs (lncRNAs) have a correlation with the prognosis of patients with HCC. Cuproptosis, a new form of regulated death of cells, is a major focus of research recently. Whereas, research on cuproptosis-associated lncRNA prognosis signature in patients with HCC is still lacking. Methods In accordance with the Cancer Genome Atlas (TCGA) database in this study, HCC patients’ clinicopathological information and RNA-seq data were obtained. The correlation of cuproptosis-associated genes (CAGs) and lncRNAs was evaluated using Pearson’s test. We screened the differentially expressed cuproptosis -associated lncRNAs (CALs) in 315 HCC and 39 normal hepatic samples. Univariate Cox regression analysis was carried out to investigate CALs correlated with prognosis. In terms of the cohort of training, a total of 24 prognostic CALs were loaded into the algorithm of least absolute shrinkage and selection operator (LASSO) to build an 8-CAL prognosis signature. The prognosis value of the signature was investigated on the basis of Kaplan–Meier (K-M) survival curve analysis and receiver operating characteristic (ROC) curve analysis. Besides, we carried out functional enrichment analyses based on Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), and the Gene Set Enrichment Analysis (GSEA) with the use of R software package. Results A prognosis signature of eight CALs was built in patients with HCC. The patients with HCC were classified as high-risk and low-risk groups according to the risk scores. This prognostic model indicated a more robust capacity in predicting survival of patients with HCC than conventional clinicopathological features. Additionally, the risk score was obviously related to T stage, tumor stage, and tumor grade. The results of the functional enrichment analyses suggested that the CAL signature played a major role in metabolism, cell cycle, and metal ion transmembrane transport processes and pathways. Conclusions The signature of eight CALs takes on an essential significance in the prognosis of HCC, which may offer novel research directions and improve individualized cancer treatment.