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Role of m6A Methylation Regulators in the Diagnosis and Subtype Classification of COPD Based on the GEO Database
Pingan Zhang1, Na Gao2, Xiaoning Li1
1Respiratory Department, the Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China.
Abstract:
N6-methyladenosine (m6A) is a prevalent mRNA modifier, yet its role in chronic obstructive pulmonary disease (COPD) remains unexplored. We sourced expression levels of m6A methylation regulators from the GSE76925 dataset. These regulators' differential expression (DEMs) predicted COPD risk via random forest and support vector machine models. Additionally, a nomogram model using DEMs estimated COPD prevalence. We employed consistent cluster analysis of m6A methylation regulators to categorise COPD samples into distinct subtypes. Analyses of immune cell infiltration in these subtypes and differential gene expression (DEGs) across m6A methylation subtypes were conducted. A cell model validated several m6A regulators and their associated pathways. Fifteen m6A methylation regulators showed differential expression and were used in random forest and support vector machine models. Eleven were selected for a nomogram model, which decision curve analysis suggested could benefit patients. Consensus cluster analysis divided the COPD samples into two subtypes: Cluster A and Cluster B. Cluster B was associated with neutrophil and eosinophil-dominated immunity, while Cluster A was linked with monocyte-dominated immunity. Validation of some research findings was achieved through cell experiments. m6A methylation regulators appear instrumental in diagnosing and classifying subtypes of COPD.
Insights
N6-methyladenosine (m6A) regulators are key in chronic obstructive pulmonary disease (COPD). This study identifies m6A regulators for COPD risk prediction and reveals distinct immune profiles in COPD subtypes, aiding diagnosis.
Area of Science:
- Molecular Biology
- Immunology
- Medical Informatics
Background:
- N6-methyladenosine (m6A) is a critical mRNA modification.
- The role of m6A in chronic obstructive pulmonary disease (COPD) is not well understood.
- Investigating m6A regulators may offer new insights into COPD pathogenesis.
Purpose of the Study:
- To explore the role of m6A methylation regulators in COPD.
- To identify m6A regulators for predicting COPD risk and prevalence.
- To classify COPD subtypes based on m6A methylation patterns and associated immune profiles.
Main Methods:
- Sourced m6A regulator expression data from the GSE76925 dataset.
- Utilized random forest and support vector machine models for risk prediction.
- Applied consensus clustering to identify COPD subtypes.
- Analyzed immune cell infiltration and differential gene expression across subtypes.
Main Results:
- Fifteen differentially expressed m6A regulators were identified.
- A nomogram model incorporating eleven m6A regulators showed potential clinical utility.
- COPD samples were classified into two subtypes (Cluster A and B) with distinct immune cell compositions (monocyte vs. neutrophil/eosinophil-dominated).
- Cell experiments validated key findings.
Conclusions:
- m6A methylation regulators are significantly involved in COPD.
- These regulators can serve as biomarkers for COPD risk prediction and diagnosis.
- Distinct m6A-driven subtypes of COPD with unique immune characteristics were identified.
- m6A regulators are instrumental in classifying COPD subtypes.
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