Exploring key genes associated with neutrophil function and neutrophil extracellular traps in heart failure: a comprehensive analysis of single-cell and bulk sequencing data

作者全名："Li, Xudong; Xu, Changhao; Li, Qiaoqiao; Shen, Qingxiang; Zeng, Long"

作者地址："[Li, Xudong] Southern Med Univ, Nanfang Hosp, Dept Cardiol, State Key Lab Organ Failure Res, Guangzhou, Peoples R China; [Xu, Changhao] Nanjing Med Univ, Affiliated Hosp 1, Dept Cardiol, Nanjing, Peoples R China; [Li, Qiaoqiao] Chongqing Med Univ, Affiliated Hosp 2, Dept Cardiol, Chongqing, Peoples R China; [Shen, Qingxiang] Univ South China, Affiliated Hosp 2, Dept Obstet & Gynecol, Hengyang, Hunan, Peoples R China; [Zeng, Long] Shangrao Peoples Hosp, Dept Cardiol, Shangrao, Jiangxi, Peoples R China"

通信作者："Zeng, L (通讯作者)，Shangrao Peoples Hosp, Dept Cardiol, Shangrao, Jiangxi, Peoples R China."

来源：FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001095428200001

JCR分区：Q1

影响因子：4.6

年份：2023

卷号：11

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：bulk RNA sequencing; heart failure; neutrophil; single-cell RNA sequencing; neutrophil extracellular traps (NET)

摘要："Background: Heart failure (HF) is a complex and heterogeneous manifestation of multiple cardiovascular diseases that usually occurs in the advanced stages of disease progression. The role of neutrophil extracellular traps (NETs) in the pathogenesis of HF remains to be explored.Methods: Bioinformatics analysis was employed to investigate general and single-cell transcriptome sequencing data downloaded from the GEO datasets. Differentially expressed genes (DEGs) associated with NETs in HF patients and healthy controls were identified using transcriptome sequencing datasets and were subsequently subjected to functional enrichment analysis. To identify potential diagnostic biomarkers, the random forest algorithm (RF) and the least absolute shrinkage and selection operator (LASSO) were applied, followed by the construction of receiver operating characteristic (ROC) curves to assess accuracy. Additionally, single-cell transcriptome sequencing data analysis identified key immune cell subpopulations in TAC (transverse aortic constriction) mice potentially involved in NETs regulation. Cell-cell communication analysis and trajectory analysis was then performed on these key cell subpopulations.Results: We identified thirteen differentially expressed genes (DEGs) associated with NET through differential analysis of transcriptome sequencing data from HF (heart failure) samples. Utilizing the Random Forest and Lasso algorithms, along with experimental validation, we successfully pinpointed four diagnostic markers (CXCR2, FCGR3B, VNN3, and FPR2) capable of predicting HF risk. Furthermore, our analysis of intercellular communication, leveraging single-cell sequencing data, highlighted macrophages and T cells as the immune cell subpopulations with the closest interactions with neutrophils. Pseudo-trajectory analysis sheds light on the differentiation states of distinct neutrophil subpopulations.Conclusion: In this study, we conducted an in-depth investigation into the functions of neutrophil subpopulations that infiltrate cardiac tissue in TAC mice. Additionally, we identified four biomarkers (CXCR2, FCGR3B, VNN3, and FPR2) associated with NETs in HF. Our findings enhance the understanding of immunology in HF."

基金机构："The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article."

基金资助正文："We would like to express our gratitude to the original research scholars who uploaded the following datasets for subsequent analysis: GSE145154(36), GSE116250(37), and GSE122930(38).r The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article."