A Novel Differentially Expressed Cuproptosis-Related lncRNAs Signature to predict the prognosis and immune characteristics of hepatocellular carcinoma

Abstract

Abstract Objective: According to a growing body of research, long non-coding RNAs (lncRNAs) participate in the progress of hepatocellular carcinoma (HCC). Cuproptosis is a distinct kind of programmed cell death, separating it from several other forms of programmed cell death that may be caused by genetic programming. Consequently, our aim was to investigate the relationship between Differentially Expressed Cuproptosis-Related lncRNAs (DECRLs) and clinical outcome and immune characteristics of HCC. Method: The Cancer Genome Atlas (TCGA) database was used to retrieve related data. The GSE101728 dataset was downloaded from the Gene Expression Omnibus (GEO) database. A list of cuproptosis-related genes (CRGs) was obtained from a recently published article in Science. Combined analysis of TCGA dataset and the GSE101728 dataset identified differentially expressed CRGs(DECRGs).We can obtain DECRLs via co-expression. Then, using DECRLs, we developed a risk prediction model using Cox regression analysis and the least absolute shrinkage selection operator (LASSO) regression analysis. To evaluate the diagnostic accuracy of this model, a Kaplan-Meier (K-M) survival analysis and a receiver operating characteristic (ROC) curve analysis were used. Next, principal component analysis (PCA) was carried out.Moreover, the relationships between the risk model and immune characteristics, somatic mutation, and drug sensitivity were also investigated. Finally Real-Time quantitative PCR(RT-qPCR) and Western Blot confirmed the expression of DECRGs or DECRLs in HCC. Results: Three high-risk DECRLs(AL031985.3,AC107959.3,MKLN1-AS) that can guide HCC prognosis and immune microenvironment were obtained through cox regression analysis.Immune functions such as APC co-inhibition,Type-II-IFN-Reponse,Parainflammation,MHC-class-I, and Tumor Immune Dysfunction and Exclusion(TIDE) score, and Tumor Mutation Burden(TMB) were significantly different in high-risk and low-risk groups.Moreover, this research also found that the IC50 values for 87 chemotherapeutic drugs varied widely across patients within high and low-risk groups.The expression of GLS at both mRNA and protein levels was significantly raised in HCC,and that of CDKN2A was dropped in HCC. The mRNA expression level of AL031985.3,AC107959.3 and MKLN1-AS was upregulated in HCC. Conclusion: The proposed 3-DECRLs that can predict clinical prognosis or guide the immune characteristics and drugs that may have a potential curative effect on HCC received in our research may play a major role in patient management and immunotherapy.