Identification of necroptosis-related signature and tumor microenvironment infiltration characteristics in lung adenocarcinoma
Identification of necroptosis-related signature and tumor microenvironment infiltration characteristics in lung adenocarcinoma
复制标题
肺腺癌中坏死性凋亡相关特征及肿瘤微环境浸润特点的鉴定
DOI：
10.1016/j.lungcan.2022.07.020
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发表时间：
2022-08-23
期刊：
影响因子：
5.3
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Liu, Taisheng;Guo, Liyi;Zhang, Jian
目的：肺癌是最常见的恶性肿瘤，也是癌症死亡的主要原因。材料和方法：从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）中获得表达数据和临床信息。在TCGA数据集中，确定了坏死性凋亡表型相关的差异表达基因（DEG）。通过整合GEO-meta数据集开发并验证了necroticscore评分。采用Kaplan-Meier法和免疫组化法（IMvigor 210队列）进一步评价风险评分的临床应用价值。结果：根据14种坏死性凋亡调节因子的异常表达，确定了3种坏死性凋亡相关模式和不同的坏死性凋亡相关基因簇。基于117个坏死性凋亡表型相关DEG获得坏死性凋亡基因组表型。建立一个坏死评分来评估每例患者的坏死性下垂模式。低necroticscore与免疫检查点表达降低、免疫检查点抑制剂应答增强和更好的临床获益相关。结论：本研究提示坏死性凋亡相关调节因子在模拟TME异质性特征中的重要作用。因此，评估坏死性凋亡模式为我们提供了更深入的了解TME，并可能指导肺癌的临床免疫治疗。
Objectives: Lung cancer remains the most common cancer and the leading cause of cancer deaths. However, the potential roles of necroptosis-related signature and tumor microenvironment (TME) in the lung adenocarcinoma (LUAD) still unknown.Materials and methods: Expression data and clinical information were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. In the TCGA dataset, necroptosis phenotype-related differentially expressed genes (DEGs) were identified. A necroticscore score was developed and validated by integrating GEO-meta datasets. The clinical value of the risk score was further evaluated using Kaplan-Meier and immunotherapeutic cohort (IMvigor210 cohort).Results: Three necroptosis-related patterns and distinct necroptosis-related gene cluster were identified based on the abnormal expression of 14 necroptosis regulators. The necroptosis genomic phenotypes were obtained based on 117 necroptosis phenotype-related DEGs. A necroticscore were constructed to evaluate necroptosis pattern of each patient. Low necroticscore was linked with decreased immune check-point expression, enhanced immune check-point inhibitor response, and better clinical benefits. Conclusion: This study suggested that the crucial roles of necroptosis-related regulators in modeling the heterogeneity of TME characteristics. Thus, assessing necroptosis patterns provided us with a deeper understanding of TME and might guide the clinical immunotherapy treatment of lung cancer.