Insulin-like growth factor binding protein 2: a core biomarker of left ventricular dysfunction in dilated
Wei Yu1,2, Hongli Gao1, Tianyang Hu3
1Department of Cardiology, The Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
Background:
RNA modifications, especially N6-methyladenosine, N1-methyladenosine and 5-methylcytosine, play an important role in the progression of cardiovascular disease. However, its regulatory function in dilated cardiomyopathy (DCM) remains to be undefined.
Methods:
In the study, key RNA modification regulators (RMRs) were screened by three machine learning models. Subsequently, a risk prediction model for DCM was developed and validated based on these important genes, and the diagnostic efficiency of these genes was assessed. Meanwhile, the relevance of these genes to clinical traits was explored. In both animal models and human subjects, the gene with the strongest connection was confirmed. The expression patterns of important genes were investigated using single-cell analysis.
Results:
A total of 4 key RMRs were identified. The risk prediction models were constructed basing on these genes which showed a good accuracy and sensitivity in both the training and test set. Correlation analysis showed that insulin-like growth factor binding protein 2 (IGFBP2) had the highest correlation with left ventricular ejection fraction (LVEF) (R = -0.49, P = 0.00039). Further validation expression level of IGFBP2 indicated that this gene was significantly upregulated in DCM animal models and patients, and correlation analysis validation showed a significant negative correlation between IGFBP2 and LVEF (R = -0.87; P = 6*10-5). Single-cell analysis revealed that this gene was mainly expressed in endothelial cells.
Conclusion:
In conclusion, IGFBP2 is an important biomarker of left ventricular dysfunction in DCM. Future clinical applications could possibly use it as a possible therapeutic target.
Insights
RNA modification regulators are key to dilated cardiomyopathy (DCM). Insulin-like growth factor binding protein 2 (IGFBP2) is identified as a biomarker for left ventricular dysfunction in DCM patients.
Area of Science:
- Molecular Biology
- Genetics
- Cardiovascular Research
Background:
- RNA modifications, including N6-methyladenosine, N1-methyladenosine, and 5-methylcytosine, are implicated in cardiovascular disease progression.
- The specific role of RNA modification regulators (RMRs) in dilated cardiomyopathy (DCM) remains largely undefined.
Purpose of the Study:
- To identify key RNA modification regulators (RMRs) involved in DCM.
- To develop and validate a risk prediction model for DCM using identified RMRs.
- To explore the clinical relevance of these RMRs in DCM.
Main Methods:
- Screening of RMRs using three machine learning models.
- Development and validation of a DCM risk prediction model based on key RMRs.
- Correlation analysis with clinical traits and validation in animal models and human subjects.
- Single-cell expression analysis of identified genes.
Main Results:
- Four key RMRs were identified, forming accurate and sensitive risk prediction models for DCM.
- Insulin-like growth factor binding protein 2 (IGFBP2) showed the strongest correlation with left ventricular ejection fraction (LVEF).
- IGFBP2 was significantly upregulated in DCM models and patients, exhibiting a negative correlation with LVEF. Single-cell analysis indicated its primary expression in endothelial cells.
Conclusions:
- IGFBP2 serves as a significant biomarker for left ventricular dysfunction in DCM.
- IGFBP2 presents potential as a therapeutic target for future clinical applications in DCM treatment.
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