Cuproptosis-related IncRNAs predict prognosis and immune reponse of lung adenocarcinoma IncRNAs predict lung adenocarcinoma

Abstract Background: lung adenocarcinoma（LUAD）accounts for 50% of lung cancers, has a high mortality and a poor prognosis. Long non-coding RNA (IncRNAs) has been suggested to play an important role in the progression of tumors. Cuproptosis is a newly discovered form of cell death that is highly investigated in which excess copper promotes the aggregation of Lipoacylated protein and the destabilisation of Fe-S cluster proteins, leading to proteotoxicity and ultimately to cell death. Therefore, the aim of this study was to explore the role of cuproptosis-related IncRNA signature in clinical prognosis prediction and immunotherapy, and the relationship with drug sensitivity.Material and Methods: Genomic, clinical, and mutational data for LUAD patients were extracted from The Cancer Genome Atlas (TCGA), cuproptosis-related genes obtained form cuproptosis-related studies. Prognostic signature was constructed by co-expression analysis and Cox regression analysis. Patients were divided into high and low risk groups and then ROC, survival, risk curves, nomogram, C-Index, independent prognostic analysis, and clinical subgroup model validation were performed to observe the value of the signature in prognosis. Subsequently, IncRNAs were analyzed for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and immune-related functions, and tumor mutation burden (TMB). Finally, we analyzed the impact of TIDE scores on immune escape and immunotherapy of IncRNAs, identifying potential drugs for LUAD and the sensitivity of the drugs.Results: A total of 16 cuproptosis-related IncRNAs were obtained (AC016747.2, LINC00205, AC006947.1, LINC00592, AC020634.2, AC026355.2, LINC02848, ZNF571-AS1, CRIM1-DT, SEPSECS-AS1, HIF1A-AS3, AC013267.1, LINC02635, AL162632.3, AC004832.5, AC032011.1.) and developed prognostic signature, we found that high-risk patients had worse overall survival (OS), progression-free survival (PFS) and higher mortality. Independent prognostic analyses, ROC, C-INDEX and nomogram demonstrate that the cuproptosis-related IncRNAs can accurately predict the prognosis of patients. nomogram and heatmap show a clear distribution of high and low risk of cuproptosis-related IncRNAs. Enrichment analysis demonstrated that the biological functions of IncRNAs are associated with the development of tumors. We also found that immune-related functions such as anti-viruses were suppressed in high-risk patients who had mutations in oncogenes, and OS was poorer in patients with high-TMB. Finally, we used TIDE to conclude that high-risk patients have a greater potential for immune escape and less effective immunotherapy, and also to identify a range of drugs that may be effective in the treatment of LUAD.Conclusion: in conclusion, the 16 cuproptosis-related IncRNAs can accurately predict the prognosis of LUAD patients and may provide new insights into clinical applications and immunotherapy.