Xiong Shan, Liu Qiming, Zhou Shenghua, Xiao Yichao
Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, China.
Xiangya School of Medicine, Central South University, Changsha, China.
Heliyon. 2023 Nov 17;9(11):e22430. doi: 10.1016/j.heliyon.2023.e22430. eCollection 2023 Nov.
The underlying molecular processes of atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) are frequently linked to increased morbidity and mortality when they co-occur. However, their underlying molecular mechanisms are questioned due to their incomplete analysis.
This study aimed to identify common differentially expressed genes (DEGs) in AF and COPD patients and investigate their potential biological functions and pathways. We hope to complement and update previous research through clearer figure presentation and different bioinformatic analysis methods with different datasets.
We used statistical analysis to identify DEGs in the expression profiles of AF and COPD patients using datasets from the Gene Expression Omnibus database. To ascertain whether the common DEGs were functionally enriched, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used. In addition, we generated protein‒protein interaction networks and identified significant hub genes. Furthermore, the hub genes were used to analyze transcription factor (TF)-gene interactions and TF-miRNA coregulatory networks, and their expression levels were validated in additional datasets.
We identified a total of 15 DEGs that were upregulated, whereas 36 were downregulated in AF and COPD patients. The DEGs were commonly expressed in both AF and COPD patients, with functional enrichment analysis revealing their involvement in metabolic processes and neuron-to-neuron synapses. We identified significant hub genes, including TGM2, ITPR1, CHL1, ALDOC, RPS3, FBLN2, NDUFS2, ITGA5, CTNNB1, RBP1, CLSTN2, FABP5, EPHA4, LDHA, and HNRNPL, and analyzed their coexpression and biological functions. TF-gene interaction and TF-miRNA coregulatory network analyses revealed the regulatory relationships of the hub genes. Additional datasets were analyzed to validate hub gene expression, and ALDOC, HNRNPL, and NDUFS2 displayed similar processes in AF and COPD patients.
In our study, we demonstrate that metabolic processes and neuron-to-neuron synaptic connections may contribute to the cooccurrence of AF and COPD. The identified hub genes and regulatory networks may act as potential biomarkers and therapeutic targets for these diseases.
心房颤动（AF）和慢性阻塞性肺疾病（COPD）的潜在分子过程在二者同时发生时，常与发病率和死亡率增加相关。然而，由于分析不完整，它们的潜在分子机制受到质疑。
本研究旨在鉴定AF和COPD患者中共同的差异表达基因（DEG），并研究其潜在的生物学功能和通路。我们希望通过更清晰的图表展示以及使用不同数据集的不同生物信息学分析方法来补充和更新先前的研究。
我们使用统计分析，利用基因表达综合数据库中的数据集，鉴定AF和COPD患者表达谱中的DEG。为确定共同的DEG是否在功能上富集，我们使用了基因本体论和京都基因与基因组百科全书通路分析。此外，我们生成了蛋白质-蛋白质相互作用网络并鉴定了重要的枢纽基因。此外，利用枢纽基因分析转录因子（TF）-基因相互作用和TF- miRNA共调控网络，并在其他数据集中验证它们的表达水平。
我们共鉴定出15个上调的DEG，而在AF和COPD患者中有36个下调的DEG。这些DEG在AF和COPD患者中均有共同表达，功能富集分析显示它们参与代谢过程和神经元间突触。我们鉴定出了重要的枢纽基因，包括转谷氨酰胺酶2（TGM2）、肌醇1,4,5-三磷酸受体1（ITPR1）、细胞粘附分子1（CHL1）、醛缩酶C（ALDOC）、核糖体蛋白S3（RPS3）、纤连蛋白2（FBLN2）、NADH脱氢酶[泛醌]铁硫蛋白2（NDUFS2）、整合素α5（ITGA5）、β-连环蛋白（CTNNB1）、视黄醇结合蛋白1（RBP1）、钙粘蛋白2（CLSTN2）、脂肪酸结合蛋白5（FABP5）、红细胞生成素受体A4（EPHA4）、乳酸脱氢酶A（LDHA）和不均一核糖核蛋白L（HNRNPL），并分析了它们的共表达和生物学功能。TF-基因相互作用和TF- miRNA共调控网络分析揭示了枢纽基因的调控关系。分析其他数据集以验证枢纽基因的表达，并且ALDOC、HNRNPL和NDUFS2在AF和COPD患者中表现出相似的过程。
在我们的研究中，我们证明代谢过程和神经元间突触连接可能促成AF和COPD的共同发生。鉴定出的枢纽基因和调控网络可能作为这些疾病的潜在生物标志物和治疗靶点。
