A Prognostic Signature of Cuproptosis-Related LncRNAs to Predict Survival and Immune Response in Esophageal Cancer

Abstract

Abstract Cuproptosis is a novel copper ion-dependent mode of programmed cell death. Aberrantly expressed lncRNAs are closely associated with the development of esophageal cancer (ESCA), yet the role played by cuproptosis and lncRNAs in ESCA remains unknown. The purpose of the study was to identify a prognostic signature of cuproptosis-related lncRNAs for predicting prognosis and immune response in ESCA. In this study, the transcriptomic and clinical data of ESCA patients were obtained from the TCGA and cuproptosis-related genes were obtained from previously published literatures, from which cuproptosis-related differentially expressed lncRNAs were identified by co-expression analysis. Selected lncRNAs were analyzed with univariate and lasso regression to construct the prognostic signature, of which we assessed the predictive power in terms of overall survival, clinical features, immune infiltration, mutational profiles, efficacy of immunotherapy, and drug sensitivity. We ultimately screened 6 cuproptosis-related prognostic lncRNAs (AC110611.2, AC125437.1, C2orf27A, EWSAT1, GK-IT1 and PRANCR) to construct a novel prognostic signature (CupRLSig) and divided the ESCA patient samples into high- and low- risk groups using the median risk score as a threshold. We demonstrated that the high- and low-risk groups differed in overall survival, clinical parameters, immune infiltration, and drug sensitivity, with the high-risk group having lower survival, more aggressive disease (tumor infiltration depth, lymph node metastasis), immunosuppressive microenvironment (M2 macrophage), and higher tumor immune dysfunction and exclusion (TIDE).The low-risk group was characterized by more antitumor immune cells (neutrophils, T cells) and enhanced immune function (T cell co − stimulation, inflammation promoting), higher tumor mutational load (TMB) and increased drug sensitivity. Gene set enrichment analysis (GSEA) results showed that tumor and immune-related pathways were obviously enriched in the low-risk group. The novel prognostic signature of cuproptosis-related lncRNAs has the potential to predict survival, immune response and drug sensitivity in ESCA, contributing to personalized clinical prediction and treatment.