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基于免疫原性细胞死亡的预测肺腺癌免疫治疗和常规治疗反应的预后模型。

Immunogenic cell death-based prognostic model for predicting the response to immunotherapy and common therapy in lung adenocarcinoma.

机构信息

Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Sci Rep. 2023 Aug 16;13(1):13305. doi: 10.1038/s41598-023-40592-w.

Abstract

Lung adenocarcinoma (LUAD) is a malignant tumor in the respiratory system. The efficacy of current treatment modalities varies greatly, and individualization is evident. Therefore, finding biomarkers for predicting treatment prognosis and providing reference and guidance for formulating treatment options is urgent. Cancer immunotherapy has made distinct progress in the past decades and has a significant effect on LUAD. Immunogenic Cell Death (ICD) can reshape the tumor's immune microenvironment, contributing to immunotherapy. Thus, exploring ICD biomarkers to construct a prognostic model might help individualized treatments. We used a lung adenocarcinoma (LUAD) dataset to identify ICD-related differentially expressed genes (DEGs). Then, these DEGs were clustered and divided into subgroups. We also performed variance analysis in different dimensions. Further, we established and validated a prognostic model by LASSO Cox regression analysis. The risk score in this model was used to evaluate prognostic differences by survival analysis. The treatment prognosis of various therapies were also predicted. LUAD samples were divided into two subgroups. The ICD-high subgroup was related to an immune-hot phenotype more sensitive to immunotherapy. The prognostic model was constructed based on six ICD-related DEGs. We found that high-risk score patients responded better to immunotherapy. The ICD prognostic model was validated as a standalone factor to evaluate the ICD subtype of individual LUAD patients, which might contribute to more effective therapies.

摘要

肺腺癌 (LUAD) 是一种呼吸系统的恶性肿瘤。目前治疗方法的疗效差异很大,具有明显的个体化特征。因此,寻找预测治疗预后的生物标志物,为制定治疗方案提供参考和指导迫在眉睫。癌症免疫疗法在过去几十年中取得了显著进展,对 LUAD 具有显著疗效。免疫原性细胞死亡 (ICD) 可以重塑肿瘤的免疫微环境,有助于免疫治疗。因此,探索 ICD 生物标志物构建预后模型可能有助于个体化治疗。我们使用肺腺癌 (LUAD) 数据集来识别与 ICD 相关的差异表达基因 (DEGs)。然后,这些 DEGs 被聚类并分为亚组。我们还在不同维度上进行了方差分析。进一步通过 LASSO Cox 回归分析建立和验证了预后模型。该模型中的风险评分用于通过生存分析评估预后差异。还预测了各种治疗方法的治疗预后。LUAD 样本被分为两个亚组。ICD-高亚组与免疫治疗更敏感的免疫热表型相关。该预后模型是基于六个与 ICD 相关的 DEGs 构建的。我们发现高风险评分患者对免疫治疗的反应更好。ICD 预后模型被验证为独立因素,用于评估个体 LUAD 患者的 ICD 亚型,这可能有助于更有效的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/420d/10432465/82f1692c2a66/41598_2023_40592_Fig1_HTML.jpg

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