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

被引:0
|
作者
Tang, Wenwu [1 ,2 ]
Wang, Zhixin [1 ]
Yuan, Xinzhu [1 ]
Chen, Liping [3 ]
Guo, Haiyang [4 ]
Qi, Zhirui [4 ]
Zhang, Ying [1 ]
Xie, Xisheng [1 ]
机构
[1] Nanchong Cent Hosp Affiliated, North Sichuan Med Coll, Dept Nephrol, Nanchong, Peoples R China
[2] Guangyuan Cent Hosp, Dept Nephrol, Guangyuan, Peoples R China
[3] North Sichuan Med Coll, Psychiat Major, Nanchong, Peoples R China
[4] North Sichuan Med Coll, Coll Clin Med, Nanchong, Peoples R China
来源
关键词
maintenance hemodialysis; heart failure; RNA-Seq; regulatory network; WGCNA; KIDNEY-DISEASE; EXPRESSION; PROGRESSION; MIGRATION; MOLECULE; MELANOMA; CELLS;
D O I
10.3389/fcvm.2024.1442238
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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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页数:14
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