Identification of hub genes for the diagnosis associated with heart failure using multiple cell death patterns

IF 3.7 2区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Hua-jing Yuan, Hui Yu, Yi-ding Yu, Xiu-juan Liu, Wen-wen Liu, Yi-tao Xue, Yan Li
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Abstract

Aims

Heart failure (HF) is an important public health problem worldwide, and programmed cell death (PCD) plays a crucial role in its pathologic process. This study aims to identify the hub genes associated with HF through PCD in order to better understand the pathogenesis of HF and improve its diagnosis and treatment.

Methods and results

The gene expression dataset of HF was obtained from the GEO database. Bioinformatics and machine learning algorithms were utilized to screen the HF key genes and PCD-related HF hub genes, and an HF diagnostic model was constructed on this. Functional enrichment analysis clarified the gene ontology and signalling pathways of HF. The immune infiltration analysis of HF was performed to explore the expression levels of immune cells in each hub gene. Through bioinformatics analysis, 95 HF key genes were obtained. Functional enrichment analysis showed that they were mainly involved in inflammation, immunomodulation and other mechanisms. DHRS11 and LRKK2 were identified as PCD-associated HF hub genes by machine learning algorithms. The hub genes were confirmed as significant biomarkers of HF in the training and validation datasets, and their constructed nomogram had effective diagnostic value. Immune infiltration analysis showed significant immune imbalance of T-cell populations, monocytes and macrophages M2 in HF.

Conclusions

In this study, DHRS11 and LRKK2 were identified as hub genes. HF diagnostic model construction and immune infiltration analyses were performed, which provided new ideas for the molecular mechanisms of HF development and treatment.

Abstract Image

利用多细胞死亡模式鉴定中心基因诊断与心力衰竭相关。
目的:心衰(HF)是一个全球性的重要公共卫生问题,而程序性细胞死亡(PCD)在其病理过程中起着至关重要的作用。本研究旨在通过PCD鉴定与HF相关的枢纽基因,以便更好地了解HF的发病机制,提高其诊断和治疗水平。方法与结果:从GEO数据库中获取HF基因表达数据集。利用生物信息学和机器学习算法筛选心衰关键基因和与pcd相关的心衰枢纽基因,并以此构建心衰诊断模型。功能富集分析阐明了HF的基因本体和信号通路。通过免疫浸润分析HF各枢纽基因免疫细胞的表达水平。通过生物信息学分析,获得95个HF关键基因。功能富集分析表明,它们主要参与炎症、免疫调节等机制。通过机器学习算法,DHRS11和LRKK2被鉴定为与pcd相关的HF枢纽基因。中心基因在训练和验证数据集中被证实是HF的重要生物标志物,其构建的nomogram具有有效的诊断价值。免疫浸润分析显示HF患者t细胞群、单核细胞和巨噬细胞M2明显免疫失衡。结论:本研究确定DHRS11和LRKK2为枢纽基因。建立心衰诊断模型并进行免疫浸润分析,为心衰发生及治疗的分子机制提供新的思路。
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来源期刊
ESC Heart Failure
ESC Heart Failure Medicine-Cardiology and Cardiovascular Medicine
CiteScore
7.00
自引率
7.90%
发文量
461
审稿时长
12 weeks
期刊介绍: ESC Heart Failure is the open access journal of the Heart Failure Association of the European Society of Cardiology dedicated to the advancement of knowledge in the field of heart failure. The journal aims to improve the understanding, prevention, investigation and treatment of heart failure. Molecular and cellular biology, pathology, physiology, electrophysiology, pharmacology, as well as the clinical, social and population sciences all form part of the discipline that is heart failure. Accordingly, submission of manuscripts on basic, translational, clinical and population sciences is invited. Original contributions on nursing, care of the elderly, primary care, health economics and other specialist fields related to heart failure are also welcome, as are case reports that highlight interesting aspects of heart failure care and treatment.
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