Insulin-like growth factor binding protein 2: a core biomarker of left ventricular dysfunction in dilated cardiomyopathy

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.

Dilated cardiomyopathy; IGFBP2; Left ventricular ejection fraction; Machine learning; RNA modifications.