DEPDC1B, CDCA2, APOBEC3B, and TYMS are potential hub genes and therapeutic targets for diagnosing dialysis patients with heart failure.

IF 2.8 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Frontiers in Cardiovascular Medicine Pub Date : 2025-01-08 eCollection Date: 2024-01-01 DOI:10.3389/fcvm.2024.1442238

Wenwu Tang, Zhixin Wang, Xinzhu Yuan, Liping Chen, Haiyang Guo, Zhirui Qi, Ying Zhang, Xisheng Xie

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Abstract

Introduction: Heart failure (HF) has a very high prevalence in patients with maintenance hemodialysis (MHD). However, there is still a lack of effective and reliable HF diagnostic markers and therapeutic targets for patients with MHD.

Methods: In this study, we analyzed transcriptome profiles of 30 patients with MHD by high-throughput sequencing. Firstly, the differential genes between HF group and control group of patients with MHD were screened. Secondly, HF-related genes were screened by WGCNA, and finally the genes intersecting the two were selected as candidate genes. Machine learning was used to identify hub gene and construct a nomogram model, which was verified by ROC curve and RT-qPCR. In addition, we further explored potential mechanism and function of hub genes in HF of patients with MHD through GSEA, immune cell infiltration analysis, drug analysis and establishment of molecular regulatory network.

Results: Totally 23 candidate genes were screened out by overlapping 673 differentially expressed genes (DEGs) and 147 key module genes, of which four hub genes (DEPDC1B, CDCA2, APOBEC3B and TYMS) were obtained by two machine learning algorithms. Through GSEA analysis, it was found that the four genes were closely related to ribosome, cell cycle, ubiquitin-mediated proteolysis. We constructed a ceRNA regulatory network, and found that 4 hub genes (TYMS, CDCA2 and DEPDC1B) might be regulated by 4 miRNAs (hsa-miR-1297, hsa-miR-4465, hsa-miR-27a-3p, hsa-miR-129-5p) and 21 lncRNAs (such as HCP5, CAS5, MEG3, HCG18). 24 small molecule drugs were predicted based on TYMS through DrugBank website. Finally, qRT-PCR experiments showed that the expression trend of biomarkers was consistent with the results of transcriptome sequencing.

Discussion: Overall, our results reveal the molecular mechanism of HF in patients with MHD and provide insights into potential diagnostic markers and therapeutic targets.

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DEPDC1B、CDCA2、APOBEC3B和TYMS是诊断透析患者心力衰竭的潜在枢纽基因和治疗靶点。

导读：心力衰竭（HF）在维持性血液透析（MHD）患者中发病率非常高。然而，对于MHD患者，目前仍缺乏有效可靠的HF诊断标志物和治疗靶点。方法：在本研究中，我们通过高通量测序分析30例MHD患者的转录组谱。首先，筛选HF组与对照组MHD患者的差异基因。其次，通过WGCNA对hf相关基因进行筛选，最终筛选出两者相交的基因作为候选基因。利用机器学习技术对hub基因进行识别，构建nomogram模型，并通过ROC曲线和RT-qPCR进行验证。此外，我们通过GSEA、免疫细胞浸润分析、药物分析和分子调控网络的建立，进一步探讨hub基因在MHD患者HF中的潜在机制和功能。结果：通过重叠673个差异表达基因（DEGs）和147个关键模块基因，共筛选出23个候选基因，其中通过两种机器学习算法获得4个枢纽基因（DEPDC1B、CDCA2、APOBEC3B和TYMS）。通过GSEA分析发现，这4个基因与核糖体、细胞周期、泛素介导的蛋白水解密切相关。我们构建了ceRNA调控网络，发现4个枢纽基因（TYMS、CDCA2和DEPDC1B）可能被4个miRNAs （hsa-miR-1297、hsa-miR-4465、hsa-miR-27a-3p、hsa-miR-129-5p）和21个lncRNAs （HCP5、CAS5、MEG3、HCG18）调控。通过DrugBank网站对24种小分子药物进行了基于TYMS的预测。最后，qRT-PCR实验表明，生物标志物的表达趋势与转录组测序结果一致。讨论：总的来说，我们的研究结果揭示了MHD患者HF的分子机制，并为潜在的诊断标志物和治疗靶点提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Cardiovascular Medicine Medicine-Cardiology and Cardiovascular Medicine

CiteScore

3.80

自引率

11.10%

发文量

3529

审稿时长

14 weeks

期刊介绍： Frontiers? Which frontiers? Where exactly are the frontiers of cardiovascular medicine? And who should be defining these frontiers? At Frontiers in Cardiovascular Medicine we believe it is worth being curious to foresee and explore beyond the current frontiers. In other words, we would like, through the articles published by our community journal Frontiers in Cardiovascular Medicine, to anticipate the future of cardiovascular medicine, and thus better prevent cardiovascular disorders and improve therapeutic options and outcomes of our patients.