通过促进 MDSCs 的扩增和抑制功能，PLA2G7 作为 COPD 免疫相关生物标志物的生物信息学分析。

Bioinformatics analysis of PLA2G7 as an immune-related biomarker in COPD by promoting expansion and suppressive functions of MDSCs.

机构信息

Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, China.

Department of Gastroenterology, Shengjing Hospital of China Medical University, China.

出版信息

Int Immunopharmacol. 2023 Jul;120:110399. doi: 10.1016/j.intimp.2023.110399. Epub 2023 Jun 2.

DOI:10.1016/j.intimp.2023.110399

PMID:37270927

Abstract

BACKGROUND

Immune mechanism is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the exact immune pathogenesis still remains unclear. This study aimed to identify the immune-related biomarkers in COPD through bioinformatics analysis and its potential molecular mechanism.

METHODS

GSE76925 was downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened, and enrichment analysis was performed. Single sample gene enrichment analysis (ssGSEA) was conducted to score the infiltration levels of immune cells. Weighted gene co-expression network analysis (WGCNA) was applied to identify trait-related modules and to further determine the key module-related DEGs. Moreover, the correlations between the key genes and clinical parameters and infiltration levels of immune cells were analyzed. Furthermore, expression of the selected one key gene, PLA2G7, the frequency of MDSCs, and the expression of MDSCs-related immunosuppressive mediators were determined among healthy, smokers and COPD patients. Finally, effects of PLA2G7 abnormal expression on the frequency of MDSCs and the expression of MDSCs-related immunosuppressive mediators were examined.

RESULTS

A total of 352 DEGs were observed. These DEGs were mainly related to RNA metabolism and positive regulation of organelle organization. In addition, the black module was the most correlated with COPD. Six key genes (ADAMDEC1, CCL19, CHIT1, MMP9, PLA2G7, and TM4SF19) were identified between the black module and DEGs. Serum Lp-PLA2 and mRNA levels of PLA2G7, MDSCs, and MDSCs-related immunosuppressive mediators were found to be upregulated in COPD patients compared to the controls. The expression of PLA2G7 represented positive impact on the frequency of MDSCs and the expression of MDSCs-related immunosuppressive mediators.

CONCLUSION

PLA2G7 may serve as a potential immune-related biomarker contributing to the progression of COPD by promoting expansion and suppressive functions of MDSCs.

摘要

背景

免疫机制参与慢性阻塞性肺疾病（COPD）的发病机制。然而，确切的免疫发病机制仍不清楚。本研究旨在通过生物信息学分析鉴定 COPD 的免疫相关生物标志物及其潜在的分子机制。

方法

从基因表达综合数据库（GEO）下载 GSE76925。筛选差异表达基因（DEGs）并进行富集分析。进行单样本基因富集分析（ssGSEA）以评估免疫细胞浸润水平。应用加权基因共表达网络分析（WGCNA）鉴定与性状相关的模块，并进一步确定关键模块相关的 DEGs。此外，分析关键基因与临床参数和免疫细胞浸润水平的相关性。进一步，在健康人群、吸烟者和 COPD 患者中测定选定的一个关键基因 PLA2G7 的表达、MDSCs 的频率以及 MDSCs 相关免疫抑制介质的表达。最后，检测 PLA2G7 异常表达对 MDSCs 频率和 MDSCs 相关免疫抑制介质表达的影响。

结果

共观察到 352 个 DEGs。这些 DEGs 主要与 RNA 代谢和细胞器组织的正调控有关。此外，黑色模块与 COPD 相关性最强。在黑色模块和 DEGs 之间鉴定出 6 个关键基因（ADAMDEC1、CCL19、CHIT1、MMP9、PLA2G7 和 TM4SF19）。与对照组相比，COPD 患者血清 Lp-PLA2 和 PLA2G7mRNA 水平、MDSCs 及其 MDSCs 相关免疫抑制介质的表达均升高。PLA2G7 的表达对 MDSCs 的频率和 MDSCs 相关免疫抑制介质的表达呈正影响。