Human Plasma Transcriptome Implicates Dysregulated S100A12 Expression: A Strong, Early-Stage Prognostic Factor in...

Area of Science:

• Cardiovascular Biology
• Molecular Diagnostics
• Genomics

Background:

• The utility of blood transcriptome analysis for identifying prognostic markers post-myocardial infarction is not well-established.
• Understanding gene expression changes is crucial for improving patient outcomes after ST-segment elevated myocardial infarction (STEMI).

Purpose of the Study:

• To identify dysregulated genes and pathways in plasma transcriptomes of STEMI patients.
• To evaluate the prognostic value of identified genes, particularly S100A12, for predicting mortality and adverse events.

Main Methods:

• Analysis of two public gene expression datasets (GSE60993, GSE61144) to identify differentially expressed genes (DEGs) in STEMI patients.
• Functional enrichment analysis (GO/KEGG) and protein-protein interaction networks to understand DEG roles.
• Verification of DEGs at transcriptional (GSE49925) and translational levels in patient samples.

Main Results:

• Identified 91 DEGs, including 15 downregulated and 76 upregulated genes.
• Discovered 12 hub genes within two key modules; six showed consistent transcriptional changes.
• S100A12 demonstrated strong predictive performance for in-hospital mortality and was an independent predictor of long-term death.

Conclusions:

• Plasma S100A12 transcriptional dysregulation is a robust early prognostic indicator in STEMI.
• While S100A12 protein levels showed lower expression in survivors, its predictive power for discharge survival and recurrent events requires further large-scale validation.