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PIK3R1, SPNB2, and CRYAB as Potential Biomarkers for Patients with Diabetes and Developing Acute Myocardial
Yue Zheng1,2,3,4,5, Yuheng Lang3,4,5,6, Zhenchang Qi3,4,5,6
1School of Medicine, Nankai University, Tianjin 300071, China.
Background:
Young patients with type 2 diabetes mellitus (DM) and acute myocardial infarction (AMI) have high long-term all-cause and cardiovascular mortality rates. We aimed to investigate the differentially expressed genes (DEGs) that might be potential targets for DM patients with AMI.
Methods:
Gene datasets GSE775, GSE19322, and GSE97494 were meta-analyzed to obtain DEGs of the left ventricle myocardium in infarcted mice. Gene datasets including GSE3313, GSE10617, and GSE136948 were meta-analyzed to identify DEGs in diabetes mice. A Venn diagram was used to obtain the overlapping DEGs. KEGG and GO pathway analyses were performed, and hub genes were obtained. Pivotal miRNAs were predicted and validated using the miRNA dataset in GSE114695. To investigate the cardiac function of the screened genes, a MI mouse model was constructed; echocardiogram, qPCR, and ELISA of hub genes were performed; ELISA of hub genes in human blood samples was also utilized.
Results:
A total of 67 DEGs were identified, which may be potential biomarkers for patients with DM and AMI. GO and KEGG pathway analyses were performed, which were mainly enriched in response to organic cyclic compound and PI3K-Akt signaling pathway. The expression of PIK3R1 and SPNB2 increased in the MI group and was negatively correlated to left ventricular ejection fraction (LVEF), whereas that of CRYAB decreased and was positively correlated to LVEF. Patients with high CRYAB expression demonstrated a short hospital stay and the area under the curves of the three protein levels before and after treatment were 0.964, 0.982, and 0.918, suggesting that PIK3R1, SPNB2, and CRYAB may be diagnostic and prognostic biomarkers for the diabetes patients with AMI.
Conclusion:
The screened hub genes, PIK3R1, SPNB2, and CRYAB, were validated as credible molecular biomarkers and may provide a novel therapy for diabetic cardiac diseases with increased proteotoxic stress.
Insights
Identifying key genes in type 2 diabetes mellitus (DM) and acute myocardial infarction (AMI) is crucial. PIK3R1, SPNB2, and CRYAB show promise as diagnostic and prognostic biomarkers for these patients.
Area of Science:
- Cardiovascular Research
- Diabetology
- Genomics
Background:
- Type 2 diabetes mellitus (DM) and acute myocardial infarction (AMI) in young patients lead to high mortality.
- Identifying specific molecular targets is essential for improved treatment strategies.
Purpose of the Study:
- To investigate differentially expressed genes (DEGs) in young patients with DM and AMI.
- To identify potential diagnostic and prognostic molecular biomarkers for this high-risk population.
Main Methods:
- Meta-analysis of gene expression datasets (GSE775, GSE19322, GSE97494, GSE3313, GSE10617, GSE136948) to identify DEGs.
- Venn diagram analysis for overlapping DEGs, followed by KEGG and GO pathway analysis.
- Prediction and validation of pivotal microRNAs (miRNAs) and hub genes (PIK3R1, SPNB2, CRYAB) using mouse models and human blood samples.
Main Results:
- 67 DEGs were identified as potential biomarkers for DM patients with AMI.
- Pathway analysis revealed enrichment in organic cyclic compound response and PI3K-Akt signaling.
- PIK3R1 and SPNB2 expression correlated negatively with left ventricular ejection fraction (LVEF), while CRYAB correlated positively, indicating their roles in cardiac function and prognosis.
Conclusions:
- PIK3R1, SPNB2, and CRYAB were validated as credible molecular biomarkers for diabetic cardiac diseases.
- These genes may offer novel therapeutic targets for managing proteotoxic stress in diabetic cardiovascular conditions.
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