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通过综合生物信息学分析探索糖酵解基因参与肺动脉高压的机制。

Exploring the mechanisms of glycolytic genes involvement in pulmonary arterial hypertension through integrative bioinformatics analysis.

机构信息

Department of cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.

出版信息

J Cell Mol Med. 2024 Jun;28(11):e18447. doi: 10.1111/jcmm.18447.

Abstract

The purpose of this study was to identify the mechanisms underlying the involvement of glycolytic genes in pulmonary arterial hypertension (PAH). This study involved downloading 3 datasets from the GEO database at the National Center for Biotechnology Information. The datasets were processed to obtain expression matrices for analysis. Genes involved in glycolysis-related pathways were obtained, and genes related to glycolysis were selected based on significant differences in expression. Gene Ontology functional annotation analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and GSEA enrichment analysis were performed on the DEGs. Combining LASSO regression with SVM-RFE machine learning technology, a PAH risk prediction model based on glycolysis related gene expression was constructed, and CIBERSORTx technology was used to analyse the immune cell composition of PAH patients. Gene enrichment analysis revealed that the DEGs work synergistically across multiple biological pathways. A total of 6 key glycolysis-related genes were selected using LASSO regression and SVM. A bar plot was constructed to evaluate the weights of the key genes and predict the risk of PAH. The clinical application value and predictive accuracy of the model were assessed. Immunological feature analysis revealed significant correlations between key glycolysis-related genes and the abundances of different immune cell types. The glycolysis genes (ACSS2, ALAS2, ALDH3A1, ADOC3, NT5E, and TALDO1) identified in this study play important roles in the development of pulmonary arterial hypertension, providing new evidence for the involvement of glycolysis in PAH.

摘要

本研究旨在探讨糖酵解基因参与肺动脉高压(PAH)的机制。本研究从美国国立生物技术信息中心的 GEO 数据库下载了 3 个数据集。对数据集进行处理,获得用于分析的表达矩阵。获取与糖酵解相关途径相关的基因,并根据表达差异显著选择与糖酵解相关的基因。对差异表达基因(DEGs)进行基因本体论功能注释分析、京都基因与基因组百科全书通路富集分析和 GSEA 富集分析。结合 LASSO 回归和 SVM-RFE 机器学习技术,构建基于糖酵解相关基因表达的 PAH 风险预测模型,并使用 CIBERSORTx 技术分析 PAH 患者的免疫细胞组成。基因富集分析表明,DEGs 在多个生物学途径中协同作用。使用 LASSO 回归和 SVM 共筛选出 6 个关键糖酵解相关基因。构建条形图以评估关键基因的权重并预测 PAH 的风险。评估了模型的临床应用价值和预测准确性。免疫特征分析表明,关键糖酵解相关基因与不同免疫细胞类型的丰度之间存在显著相关性。本研究中鉴定的糖酵解基因(ACSS2、ALAS2、ALDH3A1、ADOC3、NT5E 和 TALDO1)在肺动脉高压的发生发展中起重要作用,为糖酵解参与 PAH 提供了新的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b6/11149494/c4fca5620004/JCMM-28-e18447-g005.jpg

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