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

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

doi:10.3389/fcvm.2024.1442238

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

Front Cardiovasc Med. 2025 Jan 8:11:1442238. doi: 10.3389/fcvm.2024.1442238. eCollection 2024.

Authors

Wenwu Tang^#^{1

2}, Zhixin Wang^#¹, Xinzhu Yuan^#¹, Liping Chen³, Haiyang Guo⁴, Zhirui Qi⁴, Ying Zhang¹, Xisheng Xie¹

Affiliations

¹ Department of Nephrology, Nanchong Central Hospital Affiliated to North Sichuan Medical College, Nanchong, China.
² Department of Nephrology, Guangyuan Central Hospital, Guangyuan, China.
³ Psychiatry Major, North Sichuan Medical College, Nanchong, China.
⁴ College of Clinical Medicine, North Sichuan Medical College, Nanchong, China.

^# Contributed equally.

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.

Keywords: RNA-Seq; WGCNA; heart failure; maintenance hemodialysis; regulatory network.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the Sichuan Provincial Administration of Traditional Chinese Medicine Research Fund (2020JC0079); Sichuan Provincial Department of Science and Technology Research Special Fund (2021YFS0259); Nanchong Science and Technology Plan Project (22JCYJPT0005); Nanchong Science and Technology Plan Project (22JCYJPT0011).