基于中性粒细胞胞外陷阱的肺腺癌分子亚型和预后特征的鉴定和验证。

IF 2.3 4区 医学 Q3 ONCOLOGY
Yanhua Zuo, Guangyi Leng, Ping Leng
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引用次数: 0

摘要

背景:中性粒细胞胞外陷阱(NETs)是由dna -组蛋白复合物和从活化的中性粒细胞中突出的蛋白质组成的纤维网络。越来越多的证据强调了NETs在肿瘤进展和扩散中的重要作用。然而,关于net在LUAD中的作用的系统研究有限。方法:利用TCGA数据库对nets相关差异表达基因及其突变图谱进行鉴定。采用一致聚类分析确定与nets相关的LUAD亚型。采用LASSO算法构建预测特征。另外,采用GSE30219和GSE31210进行独立验证。我们还利用多个miRNA和lncRNA数据库构建了lncRNA-miRNA- mrna调控轴。结果:共识聚类确定了LUAD中两个与nets相关的聚类。NETs评分高与总体生存率高、免疫细胞浸润丰富、免疫应答信号通路活性高相关。筛选6个具有显著预后价值的net相关基因(G0S2、KCNJ15、S100A12、AKT2、CTSG和HMGB1)以建立预后标志。低风险的LUAD患者在训练集和验证集的总生存率均显著提高。此外,nets相关风险评分和临床分期可作为LUAD患者的独立预后因素。风险评分与肿瘤免疫微环境有显著相关。我们还发现了可能参与LUAD进展的lncRNA BCYRN1/miR-3664-5p/CTSG调控轴。结论:基于nets相关基因,我们发现了LUAD的两种分子亚型和预后特征。这种分层可以为估计LAUD患者的预后和免疫治疗提供更多的依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Identification and validation of molecular subtype and prognostic signature for lung adenocarcinoma based on neutrophil extracellular traps.

Identification and validation of molecular subtype and prognostic signature for lung adenocarcinoma based on neutrophil extracellular traps.

Identification and validation of molecular subtype and prognostic signature for lung adenocarcinoma based on neutrophil extracellular traps.

Identification and validation of molecular subtype and prognostic signature for lung adenocarcinoma based on neutrophil extracellular traps.

Background: Neutrophil Extracellular Traps (NETs) are fibrous networks made of DNA-histone complexes and proteins protruded from activated neutrophils. Accumulating evidences have highlighted the vital role of NETs in tumor progression and diffusion. However, limited systematic studies regarding the role of NETs in LUAD have been performed. Methods: Differentially expressed NETs-related genes and their mutation landscape were identified with TCGA database. Consensus clustering analysis was performed to determine the NETs-related subtypes of LUAD. LASSO algorithm was employed to construct a prognostic signature. Moreover, GSE30219 and GSE31210 were used as independent validation. We also constructed a lncRNA-miRNA-mRNA regulatory axis with several miRNA and lncRNA databases. Results: Consensus clustering identified two NETs-related clusters in LUAD. High NETs score was correlated with a favorable overall survival, abundant immune cell infiltration, and high activity of immune response signal pathways. Six NET-related genes (G0S2, KCNJ15, S100A12, AKT2, CTSG, and HMGB1) with significant prognostic value were screened to develop a prognostic signature. LUAD patients with low-risk had a significantly favorable overall survival both in the training set and validation set. Moreover, NETs-related risk score and clinical stage could act as an independent prognostic factor for LUAD patients. Significant correlation was obtained between risk score and tumor immune microenvironment. We also identified lncRNA BCYRN1/miR-3664-5p/CTSG regulatory axis that may be involved in the progression of LUAD. Conclusion: We developed two molecular subtypes and a prognostic signature for LUAD based on NETs-related genes. This stratification could provide more evidences for estimating the prognosis and immunotherapy of LAUD patients.

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来源期刊
CiteScore
6.30
自引率
0.00%
发文量
134
审稿时长
4-8 weeks
期刊介绍: Pathology & Oncology Research (POR) is an interdisciplinary Journal at the interface of pathology and oncology including the preclinical and translational research, diagnostics and therapy. Furthermore, POR is an international forum for the rapid communication of reviews, original research, critical and topical reports with excellence and novelty. Published quarterly, POR is dedicated to keeping scientists informed of developments on the selected biomedical fields bridging the gap between basic research and clinical medicine. It is a special aim for POR to promote pathological and oncological publishing activity of colleagues in the Central and East European region. The journal will be of interest to pathologists, and a broad range of experimental and clinical oncologists, and related experts. POR is supported by an acknowledged international advisory board and the Arányi Fundation for modern pathology.
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