DEPDC1B, CDCA2, APOBEC3B, and TYMS are potential hub genes and therapeutic targets for diagnosing dialysis patients with heart failure
IntroductionHeart 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.MethodsIn this study, we analyzed transcriptome profiles of 30 patie...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2024.1442238/full |
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| author | Wenwu Tang Wenwu Tang Zhixin Wang Xinzhu Yuan Liping Chen Haiyang Guo Zhirui Qi Ying Zhang Xisheng Xie |
| author_facet | Wenwu Tang Wenwu Tang Zhixin Wang Xinzhu Yuan Liping Chen Haiyang Guo Zhirui Qi Ying Zhang Xisheng Xie |
| author_sort | Wenwu Tang |
| collection | DOAJ |
| description | IntroductionHeart 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.MethodsIn 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.ResultsTotally 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.DiscussionOverall, our results reveal the molecular mechanism of HF in patients with MHD and provide insights into potential diagnostic markers and therapeutic targets. |
| format | Article |
| id | doaj-art-cc1775cc8a6c4ab79fded2c19be8400c |
| institution | DOAJ |
| issn | 2297-055X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj-art-cc1775cc8a6c4ab79fded2c19be8400c2025-08-20T02:43:49ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-01-011110.3389/fcvm.2024.14422381442238DEPDC1B, CDCA2, APOBEC3B, and TYMS are potential hub genes and therapeutic targets for diagnosing dialysis patients with heart failureWenwu Tang0Wenwu Tang1Zhixin Wang2Xinzhu Yuan3Liping Chen4Haiyang Guo5Zhirui Qi6Ying Zhang7Xisheng Xie8Department of Nephrology, Nanchong Central Hospital Affiliated to North Sichuan Medical College, Nanchong, ChinaDepartment of Nephrology, Guangyuan Central Hospital, Guangyuan, ChinaDepartment of Nephrology, Nanchong Central Hospital Affiliated to North Sichuan Medical College, Nanchong, ChinaDepartment of Nephrology, Nanchong Central Hospital Affiliated to North Sichuan Medical College, Nanchong, ChinaPsychiatry Major, North Sichuan Medical College, Nanchong, ChinaCollege of Clinical Medicine, North Sichuan Medical College, Nanchong, ChinaCollege of Clinical Medicine, North Sichuan Medical College, Nanchong, ChinaDepartment of Nephrology, Nanchong Central Hospital Affiliated to North Sichuan Medical College, Nanchong, ChinaDepartment of Nephrology, Nanchong Central Hospital Affiliated to North Sichuan Medical College, Nanchong, ChinaIntroductionHeart 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.MethodsIn 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.ResultsTotally 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.DiscussionOverall, our results reveal the molecular mechanism of HF in patients with MHD and provide insights into potential diagnostic markers and therapeutic targets.https://www.frontiersin.org/articles/10.3389/fcvm.2024.1442238/fullmaintenance hemodialysisheart failureRNA-Seqregulatory networkWGCNA |
| spellingShingle | Wenwu Tang Wenwu Tang Zhixin Wang Xinzhu Yuan Liping Chen Haiyang Guo Zhirui Qi Ying Zhang Xisheng Xie DEPDC1B, CDCA2, APOBEC3B, and TYMS are potential hub genes and therapeutic targets for diagnosing dialysis patients with heart failure Frontiers in Cardiovascular Medicine maintenance hemodialysis heart failure RNA-Seq regulatory network WGCNA |
| title | DEPDC1B, CDCA2, APOBEC3B, and TYMS are potential hub genes and therapeutic targets for diagnosing dialysis patients with heart failure |
| title_full | DEPDC1B, CDCA2, APOBEC3B, and TYMS are potential hub genes and therapeutic targets for diagnosing dialysis patients with heart failure |
| title_fullStr | DEPDC1B, CDCA2, APOBEC3B, and TYMS are potential hub genes and therapeutic targets for diagnosing dialysis patients with heart failure |
| title_full_unstemmed | DEPDC1B, CDCA2, APOBEC3B, and TYMS are potential hub genes and therapeutic targets for diagnosing dialysis patients with heart failure |
| title_short | DEPDC1B, CDCA2, APOBEC3B, and TYMS are potential hub genes and therapeutic targets for diagnosing dialysis patients with heart failure |
| title_sort | depdc1b cdca2 apobec3b and tyms are potential hub genes and therapeutic targets for diagnosing dialysis patients with heart failure |
| topic | maintenance hemodialysis heart failure RNA-Seq regulatory network WGCNA |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2024.1442238/full |
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