Construction Of A Cuproptosis-related Long Non-coding RNAs Model That Predicts The Prognostic Status Of Esophageal Cancer Patients

Background:The total serum concentration of copper increases in multiple kinds of malignant tumors,which is related to tumor occurrence and development.As a newly discovered cell death mechanism,cuproptosis plays an important role in the prognosis of many kinds of tumors.Biologically,non-coding RNA(nc RNA)includes two categories,one is small nc RNA shorter than 200 bp,and the other is long non-coding RNA(lnc RNA)longer than 200 bp,which can regulate the key pathways of tumor through its effects on transcription,post-transcription,epigenetic level,chromatin remodeling and DNA methylation.The purpose of this study is to explore the relationship between cuproptosis-related genes,lnc RNA and esophageal cancer,and establish a lnc RNA prognostic risk model related to cuproptosis genes of esophageal cancer.Method:In this study,RNA-seq transcriptome data,clinical data and tumor mutation data of esophageal cancer patients were downloaded from TCGA database.Then a lnc RNA prognostic model related to cuproptosis genes of esophageal cancer was constructed by regression(LASSO-COX)analysis,and its prognostic performance was verified.Verification includes drawing receiver operator characteristic curve(ROC)and survival curve,performing principal components analysis(PCA)on the research data,and analyzing the difference of progression-free survival(PFS)between the high-and low-risk groups.By combining the prognostic model with other clinical characteristics,nomogram was constructed,which is convenient to apply the prognostic model to the clinic.Then this study analyzed the differentially expressed genes between the high-and low-risk groups,and explored the enrichment of differentially expressed genes in the high-and low-risk groups by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and gene ontology(GO)annotation.Finally,the tumor mutation burden(TMB),immune cell infiltration and potential therapeutic drugs in the high-and low-risk groups of esophageal cancer based on the prognostic model were explored.Results:In this study,the prognostic model contains four cuproptosis-related lnc RNA,namely UGDHAS1,TMEM161B-AS1,ALMS1-IT1 and AC011773.1.Follow-up analysis showed that patients in the high-risk group had lower survival rate than the low-risk group.The esophageal cancer prognosis model constructed in this study can accurately predict the 1-,3-,5-year survival rate of patients with esophageal cancer and is an independent prognostic factor for esophageal cancer.PCA showed a high degree of differentiation between the high-risk group and the low-risk group,and the cuproptosis-related lnc RNA used to prognosis model effectively divided esophageal cancer patients into two groups.The nomogram constructed by combining other clinical traits and prognostic model also showed good performance in evaluating survival.Subsequent GO enrichment analysis showed that in the biological processes category(BP),genes were mainly enriched in muscle system process,muscle contraction and developmental maturation.In the cell component category(CC),genes were mainly enriched in cell-cell junction and contractile fiber.In the molecular functional category(MF),genes were enriched in extracellular matrix structural constituent.In the KEGG enrichment analysis,the genes were enriched in muscle system process,muscle contraction and cell maturation.TMB analysis showed that patients in the high-risk group had higher TMB than patients in the low-risk group.In terms of immune cell infiltration,we found that there were significant differences in Type II IFN Reponse,APC co-inhibition,APC co-stimulation,CCR and T cell co-stimulation infiltration between the high-and low-risk groups.Then a potential therapeutic drug NSC-207895 for esophageal cancer was screened,which has potential therapeutic value for patients with esophageal cancer.Conclusion:In this study,we constructed a lnc RNA prognostic model of esophageal cancer containing four cuproptosis-related lnc RNA,which can improve the overall survival prediction accuracy of esophageal cancer and has potential value in the immunotherapy of esophageal cancer.