Identification of molecular subtypes of coronary artery disease based on ferroptosis- and necroptosis-related genes
Aim: Coronary artery disease (CAD) is a heterogeneous disorder with high morbidity, mortality, and healthcare costs, representing a major burden on public health. Here, we aimed to improve our understanding of the genetic drivers of ferroptosis and necroptosis and the clustering of gene expression i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.870222/full |
| _version_ | 1811183541267988480 |
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| author | Wen-Pan Liu Wen-Pan Liu Peng Li Xu Zhan Lai-Hao Qu Tao Xiong Fang-Xia Hou Jun-Kui Wang Na Wei Fu-Qiang Liu |
| author_facet | Wen-Pan Liu Wen-Pan Liu Peng Li Xu Zhan Lai-Hao Qu Tao Xiong Fang-Xia Hou Jun-Kui Wang Na Wei Fu-Qiang Liu |
| author_sort | Wen-Pan Liu |
| collection | DOAJ |
| description | Aim: Coronary artery disease (CAD) is a heterogeneous disorder with high morbidity, mortality, and healthcare costs, representing a major burden on public health. Here, we aimed to improve our understanding of the genetic drivers of ferroptosis and necroptosis and the clustering of gene expression in CAD in order to develop novel personalized therapies to slow disease progression.Methods: CAD datasets were obtained from the Gene Expression Omnibus. The identification of ferroptosis- and necroptosis-related differentially expressed genes (DEGs) and the consensus clustering method including the classification algorithm used km and distance used spearman were performed to differentiate individuals with CAD into two clusters (cluster A and cluster B) based expression matrix of DEGs. Next, we identified four subgroup-specific genes of significant difference between cluster A and B and again divided individuals with CAD into gene cluster A and gene cluster B with same methods. Additionally, we compared differences in clinical information between the subtypes separately. Finally, principal component analysis algorithms were constructed to calculate the cluster-specific gene score for each sample for quantification of the two clusters.Results: In total, 25 ferroptosis- and necroptosis-related DEGs were screened. The genes in cluster A were mostly related to the neutrophil pathway, whereas those in cluster B were mostly related to the B-cell receptor signaling pathway. Moreover, the subgroup-specific gene scores and CAD indices were higher in cluster A and gene cluster A than in cluster B and gene cluster B. We also identified and validated two genes showing upregulation between clusters A and B in a validation dataset.Conclusion: High expression of CBS and TLR4 was related to more severe disease in patients with CAD, whereas LONP1 and HSPB1 expression was associated with delayed CAD progression. The identification of genetic subgroups of patients with CAD may improve clinician knowledge of disease pathogenesis and facilitate the development of methods for disease diagnosis, classification, and prognosis. |
| first_indexed | 2024-04-11T09:47:14Z |
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| id | doaj.art-4c53eed7c40243e9ad949f1f4ebae957 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T09:47:14Z |
| publishDate | 2022-09-01 |
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| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-4c53eed7c40243e9ad949f1f4ebae9572022-12-22T04:30:55ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.870222870222Identification of molecular subtypes of coronary artery disease based on ferroptosis- and necroptosis-related genesWen-Pan Liu0Wen-Pan Liu1Peng Li2Xu Zhan3Lai-Hao Qu4Tao Xiong5Fang-Xia Hou6Jun-Kui Wang7Na Wei8Fu-Qiang Liu9Cardiovascular Department, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, ChinaDepartment of Cardiothoracic Surgery, The First People’s Hospital of Kunming City and Ganmei Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Surgery, Nanzhao County People’s Hospital, Nanyang, Henan, ChinaDepartment of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Cardiothoracic Surgery, Yan’an Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Cardiothoracic Surgery, Yan’an Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaCardiovascular Department, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, ChinaCardiovascular Department, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, ChinaCardiovascular Department, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, ChinaCardiovascular Department, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, ChinaAim: Coronary artery disease (CAD) is a heterogeneous disorder with high morbidity, mortality, and healthcare costs, representing a major burden on public health. Here, we aimed to improve our understanding of the genetic drivers of ferroptosis and necroptosis and the clustering of gene expression in CAD in order to develop novel personalized therapies to slow disease progression.Methods: CAD datasets were obtained from the Gene Expression Omnibus. The identification of ferroptosis- and necroptosis-related differentially expressed genes (DEGs) and the consensus clustering method including the classification algorithm used km and distance used spearman were performed to differentiate individuals with CAD into two clusters (cluster A and cluster B) based expression matrix of DEGs. Next, we identified four subgroup-specific genes of significant difference between cluster A and B and again divided individuals with CAD into gene cluster A and gene cluster B with same methods. Additionally, we compared differences in clinical information between the subtypes separately. Finally, principal component analysis algorithms were constructed to calculate the cluster-specific gene score for each sample for quantification of the two clusters.Results: In total, 25 ferroptosis- and necroptosis-related DEGs were screened. The genes in cluster A were mostly related to the neutrophil pathway, whereas those in cluster B were mostly related to the B-cell receptor signaling pathway. Moreover, the subgroup-specific gene scores and CAD indices were higher in cluster A and gene cluster A than in cluster B and gene cluster B. We also identified and validated two genes showing upregulation between clusters A and B in a validation dataset.Conclusion: High expression of CBS and TLR4 was related to more severe disease in patients with CAD, whereas LONP1 and HSPB1 expression was associated with delayed CAD progression. The identification of genetic subgroups of patients with CAD may improve clinician knowledge of disease pathogenesis and facilitate the development of methods for disease diagnosis, classification, and prognosis.https://www.frontiersin.org/articles/10.3389/fgene.2022.870222/fullcoronary artery diseaseferroptosisnecroptosissubgroupsingle-sample gene set enrichment analysis |
| spellingShingle | Wen-Pan Liu Wen-Pan Liu Peng Li Xu Zhan Lai-Hao Qu Tao Xiong Fang-Xia Hou Jun-Kui Wang Na Wei Fu-Qiang Liu Identification of molecular subtypes of coronary artery disease based on ferroptosis- and necroptosis-related genes Frontiers in Genetics coronary artery disease ferroptosis necroptosis subgroup single-sample gene set enrichment analysis |
| title | Identification of molecular subtypes of coronary artery disease based on ferroptosis- and necroptosis-related genes |
| title_full | Identification of molecular subtypes of coronary artery disease based on ferroptosis- and necroptosis-related genes |
| title_fullStr | Identification of molecular subtypes of coronary artery disease based on ferroptosis- and necroptosis-related genes |
| title_full_unstemmed | Identification of molecular subtypes of coronary artery disease based on ferroptosis- and necroptosis-related genes |
| title_short | Identification of molecular subtypes of coronary artery disease based on ferroptosis- and necroptosis-related genes |
| title_sort | identification of molecular subtypes of coronary artery disease based on ferroptosis and necroptosis related genes |
| topic | coronary artery disease ferroptosis necroptosis subgroup single-sample gene set enrichment analysis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.870222/full |
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