Department of Translational Medicine, The First Hospital of Jilin University, Changchun, China.
College of Basic Medical Sciences, Jilin University, Changchun, China.
Oncol Res. 2023 Jul 21;31(5):753-767. doi: 10.32604/or.2023.029287. eCollection 2023.
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.
肺腺癌(LUAD)是癌症相关死亡的主要原因,全球每年因此导致的死亡人数超过 100 万。免疫原性细胞死亡(ICD)引发适应性免疫反应。然而,ICD 相关长链非编码 RNA(lncRNA)在 LUAD 中的作用尚不清楚。在这项研究中,我们研究了 LUAD 肿瘤微环境的特征、与 ICD 相关的 lncRNA 的预后意义以及可能的化疗药物的半最大抑制浓度(IC50)。我们使用单变量 Cox 回归对预后 lncRNA 进行排序,并基于它们构建风险特征。然后,我们验证了模型的准确性并生成了列线图。此外,我们进行了免疫微环境分析、体细胞突变计算、肿瘤免疫功能障碍和排除(TIDE)分析以及抗癌药物 IC50 预测。最小绝对收缩和选择算子 Cox 回归确定了 27 个与 ICD 相关的预后 lncRNA,并使用 10 个与 ICD 相关的 lncRNA 构建了独特的风险特征。风险评分被确认为生存的可靠预测指标,具有最高的 c 指数评分。该特征具有显著的预测性能和临床适用性,能够准确预测 LUAD 的总生存期。此外,lncRNA 特征与免疫细胞浸润密切相关。我们还分析了风险评分、肿瘤浸润免疫细胞与预后之间的相关性,并在低风险患者中发现了高免疫和 ESTIMATE 评分。此外,我们观察到高风险患者中检查点基因表达升高和 TIDE 评分降低,表明免疫治疗反应良好。最后,高风险患者易受抗癌药物影响。因此,我们构建的由 10 个与 ICD 相关的 lncRNA 组成的独特风险特征,能够反映 LUAD 肿瘤免疫微环境的特征,预测患者的总生存期,并指导个体化治疗。