Identification of a Common Different Gene Expression Signature in Ischemic Cardiomyopathy

Q: What are the key findings of this study?

Gene expression profiling of 227 ischemic cardiomyopathy and 162 control samples identified 255 common differentially expressed genes (93 upregulated, 162 downregulated; adjusted p<0.05).

Q: What is the clinical evidence from this study?

Population: Ischemic cardiomyopathy (ICM) and heart failure (n=389). Intervention: Ischemic cardiomyopathy (gene expression profiling) vs. Control donor heart samples. Primary outcome: Common differentially expressed genes (DEGs) across four GEO datasets (p=<0.05).

Q: What does this research mean for the field?

Ischemic cardiomyopathy is characterized by a shared transcriptomic profile of 255 differentially expressed genes prominently involving immune and cytokine signaling pathways and Y-chromosome-linked genes. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To identify genes and biological pathways that are significantly altered during the development of heart failure caused by ischemic cardiomyopathy.

Yana Li; Jiang Qiu; Zhiwen Ding; Guijian Liu; Peng Yu; Guoliang Jiang; Ziqing Yu; Chunjie Yang; Juying Qian; Hong Jiang; Yunzeng Zou

doi:10.3390/genes9010056

January 22, 2018GenesOpen Access

Identification of a Common Different Gene Expression Signature in Ischemic Cardiomyopathy

View Full Paper

Ask AI

Bookmark

Share

Key result

Transcriptional profiling reveals ~255 differentially expressed genes distinguishing ischemic cardiomyopathy from normal myocardium.

P<0.05
n=389

Figures

Key Points

To identify genes and biological pathways that are significantly altered during the development of heart failure caused by ischemic cardiomyopathy.
Analyzed left ventricular microarray datasets from 162 control samples and 227 ischemic cardiomyopathy patients across four Gene Expression Omnibus series.
Performed Gene Ontology via PANTHER, pathway enrichment via Reactome, and protein-protein interaction network construction using STRING and Cytoscape.
Validated top differentially expressed genes using real-time polymerase chain reaction (RT-PCR) in human heart tissue.
Identified 255 common differentially expressed genes (93 upregulated and 162 downregulated), primarily clustered in catalytic activity (39.4%) and protein binding (38.0%).
Demonstrated that the top five upregulated genes were located on chromosome Y (EIF1AY, UTY, USP9Y, RPS4Y1, and DDX3Y), while four of the top five downregulated genes (SERPINA3, S100A8, FCN3, and CD163) mediated immune and inflammation signaling (p < 0.05).

Structured PICO

P

Population

389 total myocardial tissue samples (227 ischemic cardiomyopathy patients and 162 control samples) from four GEO microarray datasets (excluding ages <20 and >80), plus 6 male human left ventricular tissue samples (3 NYHA class IV ICM patients with LVEF <=40% and 3 unused donor controls) for RT-PCR validation.

E

Exposure

Ischemic cardiomyopathy (ICM) transcriptional profiling via microarray reanalysis (GEO2R) and RT-PCR validation

C

Comparator

Control normal/unused donor left ventricular myocardium samples

O

Outcome

Identification of common differentially expressed genes (DEGs, adjusted p<0.05), gene ontology (GO) terms, Reactome pathway enrichment, and protein-protein interaction (PPI) hub genessurrogate

Main Result

p-value: p=<0.05

Transcriptomic reanalysis of ischemic cardiomyopathy myocardium reveals 255 conserved differentially expressed genes heavily enriched in cytokine/immune signaling, lipid metabolism, and Y-chromosome loci, suggesting potential molecular targets for ischemic heart failure.

Limitations

Differences in the number of genes represented across different microarray platforms (Affymetrix Human Gene 1.0 ST Array vs Affymetrix U133A Array) meant DEGs detected only in two datasets could not be included in the overall analysis.
None of the included datasets were capable of detecting the expression levels of noncoding RNAs.
Inevitable confounding factors existed, including fewer female samples in the ICM group in some datasets.
The analysis was not further stratified by age.
Different microarray platforms had varying transcript counts (28,869 in Affymetrix Human Gene 1.0 ST Array vs 22,283 in Affymetrix U133A Array), excluding DEGs only present on larger arrays from the common intersection.
None of the datasets could detect noncoding RNAs.
Confounding factors due to gender bias (fewer female samples in the ICM group in some datasets).
Lack of stratification by age.

Implication

Hypothesis-generating for immune-metabolic targets in ischemic cardiomyopathy; requires human validation before clinical consideration.

Abstract

The molecular mechanisms underlying the development of ischemic cardiomyopathy (ICM) remain poorly understood. Gene expression profiling is helpful to discover the molecular changes taking place in ICM. The aim of this study was to identify the genes that are significantly changed during the development of heart failure caused by ICM. The differentially expressed genes (DEGs) were identified from 162 control samples and 227 ICM patients. PANTHER was used to perform gene ontology (GO), and Reactome for pathway enrichment analysis. A protein-protein interaction network was established using STRING and Cytoscape. A further validation was performed by real-time polymerase chain reaction (RT-PCR). A total of 255 common DEGs was found. Gene ontology, pathway enrichment, and protein-protein interaction analysis showed that nucleic acid-binding proteins, enzymes, and transcription factors accounted for a great part of the DEGs, while immune system signaling and cytokine signaling displayed the most significant changes. Furthermore, seven hub genes and nine transcription factors were identified. Interestingly, the top five upregulated DEGs were located on chromosome Y, and four of the top five downregulated DEGs were involved in immune and inflammation signaling. Further, the top DEGs were validated by RT-PCR in human samples. Our study explored the possible molecular mechanisms of heart failure caused by ischemic heart disease.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Li et al. (2018) studied Ischemic cardiomyopathy (ICM) and heart failure (n=389). Ischemic cardiomyopathy (gene expression profiling) vs. Control donor heart samples was evaluated on Common differentially expressed genes (DEGs) across four GEO datasets (p=<0.05). Gene expression profiling of 227 ischemic cardiomyopathy and 162 control samples identified 255 common differentially expressed genes (93 upregulated, 162 downregulated; adjusted p<0.05).

synapsesocial.com/papers/6a77a7f9df493903fd1f171a https://doi.org/10.3390/genes9010056

View Full Paper

Ask AI

Bookmark

Share

Identification of a Common Different Gene Expression Signature in Ischemic Cardiomyopathy

Figures

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Identification of a Common Different Gene Expression Signature in Ischemic Cardiomyopathy

Figures

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading