Cuproptosis-related LncRNA Signatures As A Novel Prognostic Model For Head And Neck Squamous Cell Carcinoma

Objective:Head and neck squamous cell carcinoma(HNSCC)is a highly heterogeneous malignancy,which makes the prognosis of HNSCC challenging to predict.Cuproptosis is a novel type of copper dependent programmed cell death that is highly associated with mitochondrial metabolism and mediated by protein lipid acylation.It is very different from common programmed cell death patterns(apoptosis,pyroptosis,necroptosis and ferroptosis).Long non-coding ribonucleic acid(lnc RNA)is thought to be a key regulator of HNSCC development and may also influence the prognosis of patients by regulating the cuproptosis,which may be a predictor of overall survival(OS)in HNSCC.In this study,we assessed the ability of cuproptosis-related lnc RNA on the prognosis of HNSCC through bioinformatic analysis of data from TCGA database to provide a new prognosis and treatment of head and neck squamous cell carcinoma.Methods:The present study investigated the prognostic importance of lnc RNAs involved in cuproptosis through the RNA-seq matrix,and related clinical information of HNSCC patients downloaded from The Cancer Genome Atlas database,and cuproptosis-related genes(CRGs)were acquired from previous studies.Wilcoxon test were calculated based on FRGs and lnc RNA expression profiles to identify FRLs(|R~2|>0.4 and p<0.001).To construct a risk model and validate the accuracy of the results,the samples were divided into two cohorts randomly and equally.Univariate Cox regression was used to identify cuproptosis-related prognostic lnc RNAs.LASSO-Cox method was used to narrow these cuproptosis-related prognostic lnc RNAs and construct a prognostic model.Then,the prognostic model based on cuproptosis-related lnc RNAs(CRLs)was established.HNSCC samples were divided into two groups according to the median risk.Consequently,we divided patients into high-and low-risk groups based on the CRLs signature.In addition,the prognostic potential of the CRL signature was verified.We also evaluated the prognostic power of this model using Kaplan–Meier(K-M)survival curve analysis,receiver operating characteristic(ROC)curve analysis,and C index.Gene ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were conducted for functional and pathway enrichment analysis.Additionally,the gene set enrichment analysis(GSEA)was applied to identify the top five significant pathways in the high-risk and the low-risk subgroups.The difference in immune cell infiltration in the two groups of patients was evaluated using the CIBERSORT algorithm.The differences immune-related function between the high-and low-risk subsets were studied using the single-sample GSEA(ss GSEA).Lastly,we investigated the expression of the immune checkpoint genes in the two risk subgroups.Result:A 9-lnc RNA signature was identified in the TCGA train cohort utilizing the LASSO Cox regression model.The formula for ferroptosis-related prognostic risk scores for each patient was Risk score=0.0681099981526671×AC010894.1-0.16432167078626×CDKN2A-DT-0.531925811974634×ECE1-AS1+0.485754273099877×AC012184.3-0.685199328188189×AC021148.2-0.12310460657846×AC090587.1-0.0292634300508353×EP300-AS1-0.00354833963632324×AC104794.3-0.009637481201233×RAB11B-AS1.In addition,the prognostic potential of the9-CRL signature was verified.Kaplan-Meier(K-M)curve analysis demonstrated a significantly preferable prognosis in the low-risk group.The ROC curves demonstrated that the model accurately predicted patient prognosis(0.721,0.751,and 0.686 for the 1-,3-,and 5-year AUCs,respectively).The multivariate Cox regression analysis results showed that the lnc RNA signature is an independent risk factor for the OS rates.The ROC and C index show signature-based risk score exhibited a more powerful capacity for survival prediction than traditional clinicopathological features in HNSCC patients.GO and KEGG enrichment analysis showed that the differential genes between the high and low risk groups were mainly enriched in the development of immune response and immune-related pathways.Patients in the high-risk group behaved a lowerer immune check points expression,immune function activity and scores.In addition,patients from low-risk group were more sensitive to immunotherapy.Conclusion:Overall,the proposed novel 9-CRL signature can predict prognosis and assess the efficacy of immunotherapy to prolong the survival of patients with HNSCC.