Immunogenic cell death-related long noncoding RNA influences immunotherapy against lung adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths, accounting for over a million deaths worldwide annually. Immunogenic cell death (ICD) elicits an adaptive immune response. However, the role of ICD-related long noncoding RNAs (lncRNAs) in LUAD is unknown. In this study, we investigated the characteristics of the tumor microenvironment in LUAD, the prognostic significance of ICD-related lncRNAs, and the half-maximal inhibitory concentration (IC50) of possible chemotherapeutic drugs. We sorted prognostic lncRNAs using univariate Cox regression and constructed a risk signature based on them. We then confirmed the model’s accuracy and generated a nomogram. Additionally, we performed immune microenvironment analysis, somatic mutation calculation, Tumor Immune Dysfunction and Exclusion (TIDE) analysis, and anticancer pharmaceutical IC50 prediction. Least absolute shrinkage and selection operator Cox regression identified 27 prognostic lncRNAs related to ICD, and a unique risk signature using 10 ICD-related lncRNAs was constructed. The risk score was confirmed to be a reliable predictor of survival, with the highest c-index score. The signature had a remarkable predictive performance with clinical applicability and could accurately predict the overall survival in LUAD. Furthermore, the lncRNA signature was closely associated with immunocyte invasion. We also analyzed the correlation between the risk score, tumor-infiltrating immune cells, and prognosis and identified high immune and ESTIMATE scores in low-risk patients. Moreover, we observed elevated checkpoint gene expression and low TIDE scores in high-risk patients, indicating a good immunotherapy response. Finally, high-risk patients were shown to be susceptible to anticancer medications. Therefore, our unique risk signature comprising 10 ICD-related lncRNAs was demonstrated to indicate the characteristics of the tumor-immune microenvironment in LUAD, predict patients’ overall survival, and guide individualized treatment.