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Isolating Brown Adipocytes from Murine Interscapular Brown Adipose Tissue for Gene and Protein Expression Analysis
Published on: March 12, 2021
Subgroup Identification with Gene Expression Profiles of Adipose Tissue in Patients with Coronary Artery Disease
Chunying Jiang1, Rui Wang2, Bin Zong1
1Department of Cardiology, The Xuzhou School of Clinical Medicine of Nanjing Medical University; Xuzhou Central Hospital.
Insights
This study genetically classified coronary artery disease (CAD) patients into three subgroups based on adipose tissue gene expression. Subgroup III showed increased Th17 cell differentiation linked to higher BMI, suggesting personalized CAD treatments.
Area of Science:
- Genomics
- Cardiovascular Research
- Metabolomics
Background:
- Coronary artery disease (CAD) is a leading global cause of death.
- Understanding CAD subtypes' genetic basis is crucial for targeted therapies.
- Adipose tissue transcriptome profiles offer insights into CAD heterogeneity.
Purpose of the Study:
- To genetically classify coronary artery disease (CAD) patients into distinct subgroups.
- To identify subgroup-specific gene expression patterns and associated pathways.
- To explore the relationship between genetic subtypes and clinical characteristics.
Main Methods:
- Recruited 77 CAD patients and analyzed adipose tissue transcriptome data.
- Applied consensus clustering after batch effect removal to define subgroups.
- Utilized Gene Ontology, KEGG, WGCNA, GSEA, and OEA for pathway and module analysis.
Main Results:
- Identified three distinct CAD subgroups.
- Subgroup I showed upregulated protein digestion and absorption pathways.
- Subgroup II exhibited high expression of complement, coagulation, and TNF signaling pathways.
- Subgroup III displayed upregulated Th17 cell differentiation, associated with higher BMI and increased adiposity.
Conclusions:
- Genetic classification reveals distinct molecular profiles within CAD.
- Specific pathways and immune responses characterize each subgroup.
- Findings support personalized treatment strategies for CAD patients based on their genetic subtype.
Abstract:
Among many diseases, coronary artery disease (CAD) is the primary cause of mortality and morbidity worldwide. With the aim of revealing the underlying genetic characteristics of the CAD subtypes, we recruited patients with CAD and categorized them into subgroups according to the transcriptome expression profiles of the adipose tissue.With the removal of the batch effect, consensus clustering was employed to determine the subgroup numbers. Subgroup-specific genes were determined to conduct analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Weighted gene co-expression network analysis (WGCNA) revealed the subgroup-specific WGCNA modules. Moreover, gene set enrichment analysis (GSEA) was conducted. Overrepresentation enrichment analysis (OEA) of subgroup-specific signatures was also conducted to reveal the significant gene module associated with the corresponding clinical characteristics.After the removal of the batch effect, 77 CAD objects were divided into three subgroups. It was observed that the patients in subgroup III tended to be fat. After analyzing the dominant pathways of each subgroup, we discovered that the protein digestion and absorption pathway was specifically upregulated in subgroup I, which might result from the lowest proportion of the epicardial adipose tissue (EAT) sample. Moreover, subgroup II patients had genetic characteristics of high expression of complement and coagulation cascades and TNF signaling pathway. Furthermore, Th17 cell differentiation was significantly upregulated in subgroup III, indicating that Th17 cell differentiation is related to the clinical characteristics of body mass index (BMI).In conclusion, the genetic classification of CAD subjects indicated that subjects from different subgroups may exhibit specific gene expression patterns, suggesting that more personalized treatment should be applied to patients in each subgroup.
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