Significance of RNA N6-methyladenosine regulators in the diagnosis and subtype classification of coronary heart disease using the Gene Expression Omnibus database
BackgroundMany investigations have revealed that alterations in m6A modification levels may be linked to coronary heart disease (CHD). However, the specific link between m6A alteration and CHD warrants further investigation.MethodsGene expression profiles from the Gene Expression Omnibus (GEO) datab...
| Main Authors: | , , , , , |
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| Format: | Article |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1185873/full |
| _version_ | 1797656049522573312 |
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| author | Yu Jiang Yaqiang Pan Tao Long Junqing Qi Jianchao Liu Mengya Zhang |
| author_facet | Yu Jiang Yaqiang Pan Tao Long Junqing Qi Jianchao Liu Mengya Zhang |
| author_sort | Yu Jiang |
| collection | DOAJ |
| description | BackgroundMany investigations have revealed that alterations in m6A modification levels may be linked to coronary heart disease (CHD). However, the specific link between m6A alteration and CHD warrants further investigation.MethodsGene expression profiles from the Gene Expression Omnibus (GEO) databases. We began by constructing a Random Forest model followed by a Nomogram model, both aimed at enhancing our predictive capabilities on specific m6A markers. We then shifted our focus to identify distinct molecular subtypes based on the key m6A regulators and to discern differentially expressed genes between the unique m6A clusters. Following this molecular exploration, we embarked on an in-depth analysis of the biological characteristics associated with each m6A cluster, revealing profound differences between them. Finally, we delved into the identification and correlation analysis of immune cell infiltration across these clusters, emphasizing the potential interplay between m6A modification and the immune system.ResultsIn this research, 37 important m6Aregulators were identified by comparing non-CHD and CHD patients from the GSE20680, GSE20681, and GSE71226 datasets. To predict the risk of CHD, seven candidate m6A regulators (CBLL1, HNRNPC, YTHDC2, YTHDF1, YTHDF2, YTHDF3, ZC3H13) were screened using the logistic regression model. Based on the seven possible m6A regulators, a nomogram model was constructed. An examination of decision curves revealed that CHD patients could benefit from the nomogram model. On the basis of the selected relevant m6A regulators, patients with CHD were separated into two m6A clusters (cluster1 and cluster2) using the consensus clustering approach. The Single Sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT methods were used to estimate the immunological characteristics of two separate m6A Gene Clusters; the results indicated a close association between seven candidate genes and immune cell composition. The drug sensitivity of seven candidate regulators was predicted, and these seven regulators appeared in numerous diseases as pharmacological targets while displaying strong drug sensitivity.Conclusionm6A regulators play crucial roles in the development of CHD. Our research of m6A clusters may facilitate the development of novel molecular therapies and inform future immunotherapeutic methods for CHD. |
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| issn | 2297-055X |
| language | English |
| last_indexed | 2024-03-11T17:23:39Z |
| publishDate | 2023-10-01 |
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| spelling | doaj.art-5d17f402f2a64481b2b36390d880942f2023-10-19T08:02:32ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-10-011010.3389/fcvm.2023.11858731185873Significance of RNA N6-methyladenosine regulators in the diagnosis and subtype classification of coronary heart disease using the Gene Expression Omnibus databaseYu Jiang0Yaqiang Pan1Tao Long2Junqing Qi3Jianchao Liu4Mengya Zhang5Department of Cardiovascular Surgery, Yan'an Hospital affiliated to Kunming Medical University, Yunnan, ChinaDepartment of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Cardiology, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, ChinaBackgroundMany investigations have revealed that alterations in m6A modification levels may be linked to coronary heart disease (CHD). However, the specific link between m6A alteration and CHD warrants further investigation.MethodsGene expression profiles from the Gene Expression Omnibus (GEO) databases. We began by constructing a Random Forest model followed by a Nomogram model, both aimed at enhancing our predictive capabilities on specific m6A markers. We then shifted our focus to identify distinct molecular subtypes based on the key m6A regulators and to discern differentially expressed genes between the unique m6A clusters. Following this molecular exploration, we embarked on an in-depth analysis of the biological characteristics associated with each m6A cluster, revealing profound differences between them. Finally, we delved into the identification and correlation analysis of immune cell infiltration across these clusters, emphasizing the potential interplay between m6A modification and the immune system.ResultsIn this research, 37 important m6Aregulators were identified by comparing non-CHD and CHD patients from the GSE20680, GSE20681, and GSE71226 datasets. To predict the risk of CHD, seven candidate m6A regulators (CBLL1, HNRNPC, YTHDC2, YTHDF1, YTHDF2, YTHDF3, ZC3H13) were screened using the logistic regression model. Based on the seven possible m6A regulators, a nomogram model was constructed. An examination of decision curves revealed that CHD patients could benefit from the nomogram model. On the basis of the selected relevant m6A regulators, patients with CHD were separated into two m6A clusters (cluster1 and cluster2) using the consensus clustering approach. The Single Sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT methods were used to estimate the immunological characteristics of two separate m6A Gene Clusters; the results indicated a close association between seven candidate genes and immune cell composition. The drug sensitivity of seven candidate regulators was predicted, and these seven regulators appeared in numerous diseases as pharmacological targets while displaying strong drug sensitivity.Conclusionm6A regulators play crucial roles in the development of CHD. Our research of m6A clusters may facilitate the development of novel molecular therapies and inform future immunotherapeutic methods for CHD.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1185873/fullcoronary heart diseasem6A RNA methylation regulatorconsensus clusteringGene Expression Omnibus databaserisk prediction modelimmune cell infiltration |
| spellingShingle | Yu Jiang Yaqiang Pan Tao Long Junqing Qi Jianchao Liu Mengya Zhang Significance of RNA N6-methyladenosine regulators in the diagnosis and subtype classification of coronary heart disease using the Gene Expression Omnibus database Frontiers in Cardiovascular Medicine coronary heart disease m6A RNA methylation regulator consensus clustering Gene Expression Omnibus database risk prediction model immune cell infiltration |
| title | Significance of RNA N6-methyladenosine regulators in the diagnosis and subtype classification of coronary heart disease using the Gene Expression Omnibus database |
| title_full | Significance of RNA N6-methyladenosine regulators in the diagnosis and subtype classification of coronary heart disease using the Gene Expression Omnibus database |
| title_fullStr | Significance of RNA N6-methyladenosine regulators in the diagnosis and subtype classification of coronary heart disease using the Gene Expression Omnibus database |
| title_full_unstemmed | Significance of RNA N6-methyladenosine regulators in the diagnosis and subtype classification of coronary heart disease using the Gene Expression Omnibus database |
| title_short | Significance of RNA N6-methyladenosine regulators in the diagnosis and subtype classification of coronary heart disease using the Gene Expression Omnibus database |
| title_sort | significance of rna n6 methyladenosine regulators in the diagnosis and subtype classification of coronary heart disease using the gene expression omnibus database |
| topic | coronary heart disease m6A RNA methylation regulator consensus clustering Gene Expression Omnibus database risk prediction model immune cell infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1185873/full |
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