Prognostic value and immune landscapes of immunogenic cell death-associated lncRNAs in lung adenocarcinoma

Abstract

AbstractImmunogenic cell death (ICD) has been demonstrated to activate T cells to kill tumor cells, which is closely related to tumor development, and long noncoding RNAs (lncRNAs) are also involved. However, it is not known whether ICD-related lncRNAs are associated with the development of lung adenocarcinoma (LUAD). We downloaded ICD-related genes from GeneCards and the transcriptome statistics of LUAD patients from The Cancer Genome Atlas (TCGA) and subsequently developed and verified a predictive model. A successful model was used together with other clinical features to construct a nomogram for predicting patient survival. To further study the mechanism of tumor action and to guide therapy, we performed enrichment analysis, tumor microenvironment analysis, somatic mutation analysis, drug sensitivity analysis and real-time quantitative polymerase chain reaction (RT-qPCR) analysis. Nine ICD-related lncRNAs with significant prognostic relevance were selected for model construction. Survival analysis demonstrated that overall survival was substantially shorter in the high-risk group than in the low-risk group (P < 0.001). This model was predictive of prognosis across all clinical subgroups. Cox regression analysis further supported the independent prediction ability of the model. Ultimately, a nomogram depending on stage and risk score was created and showed a better predictive performance than the nomogram without the risk score. Through enrichment analysis, the enriched pathways in the high-risk group were found to be primarily associated with metabolism and DNA replication. Tumor microenvironment analysis suggested that the immune cell concentration was lower in the high-risk group. Somatic mutation analysis revealed that the high-risk group contained more tumor mutations (P = 0.00018). Tumor immune dysfunction and exclusion scores exhibited greater sensitivity to immunotherapy in the high-risk group (P < 0.001). Drug sensitivity analysis suggested that the predictive model can also be applied to the choice of chemotherapy drugs. RT-qPCR analysis also validated the accuracy of the constructed model based on nine ICD-related lncRNAs. The prognostic model constructed based on the nine ICD-related lncRNAs showed good application value in assessing prognosis and guiding clinical therapy.