College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, 100091, China; Beijing Key Laboratory of OTIR, Beijing, 100091, China.
College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, 100091, China; Hebei North Universit, Zhangjiakou, 075000, China.
Comput Biol Med. 2023 Mar;154:106621. doi: 10.1016/j.compbiomed.2023.106621. Epub 2023 Jan 31.
Chronic obstructive pulmonary disease is a kind of chronic lung disease characterized by persistent air flow obstruction, which was the third leading cause of death in China. The incidence of COPD is steadily and increasing and has been a globally sever disease. Accordingly, it is urgently needed to explore how to diagnose and treat COPD timely. This study aims to find key genes to diagnose COPD as soon as possible to avoid COPD processing and analyze immune cell infiltration between COPD early stage and late stage. Two GEO datasets were merged as the merge data for analyses. 157 DEGs were used for GSEA analysis to find the pathway between COPD early stage and late stage. Above all, gene EXPH5 stood out from the screen as the most likely candidate diagnosis biomarker of COPD indicating the late-stage by least LASSO and SVM-RFE. ROC curves of EXPH5 were applied to represent the discriminatory ability through the area under the curve which is the gold standard to evaluate the accuracy of diagnosis and survival rate. The CIBERSORT algorithm was used to assess the distribution of tissue-infiltrating immune cells between two COPD stages. The diagnosis biomarker, gene EXPH5 had a positive correlation with NK cells resting; mast cell resting, eosinophils, and negative correlation with T cell gamma delta, macrophages M1, which underscore the role of gene and immune cell infiltration. To make results more reliable, we further analyzed the gene EXPH5 expression in single-cell transcriptome data and showed again that EXPH5 genes significantly downregulated in the late stage of COPD especially in the main lung cell types AT1 and AT2. In a word, our study identified genes EXPH5 as a marker gene, which adds to the knowledge for clinical diagnosis and pharmaceutical design of COPD.
慢性阻塞性肺疾病是一种以持续性气流阻塞为特征的慢性肺部疾病，是中国第三大死亡原因。COPD 的发病率稳步上升，已成为全球性严重疾病。因此，迫切需要探索如何及时诊断和治疗 COPD。本研究旨在寻找关键基因，尽快诊断 COPD，避免 COPD 进展，并分析 COPD 早期和晚期之间的免疫细胞浸润。合并了两个 GEO 数据集作为分析的合并数据。使用 157 个差异表达基因进行 GSEA 分析，以发现 COPD 早期和晚期之间的通路。总的来说，基因 EXPH5 从筛选中脱颖而出，成为 COPD 最有可能的候选诊断生物标志物，通过最小的 LASSO 和 SVM-RFE 指示晚期。EXPH5 的 ROC 曲线用于通过曲线下面积表示区分能力，这是评估诊断准确性和生存率的金标准。CIBERSORT 算法用于评估两个 COPD 阶段之间组织浸润免疫细胞的分布。诊断生物标志物基因 EXPH5 与 NK 细胞静息呈正相关；肥大细胞静息、嗜酸性粒细胞，与 T 细胞 γδ、巨噬细胞 M1 呈负相关，突出了基因和免疫细胞浸润的作用。为了使结果更可靠，我们进一步分析了单细胞转录组数据中基因 EXPH5 的表达，再次表明 EXPH5 基因在 COPD 晚期特别是在主要肺细胞类型 AT1 和 AT2 中显著下调。总之，我们的研究确定了基因 EXPH5 作为一个标记基因，为 COPD 的临床诊断和药物设计增添了知识。
