Human Plasma Transcriptome Implicates Dysregulated S100A12 Expression: A Strong, Early-Stage Prognostic Factor in ST-Segment Elevated Myocardial Infarction: Bioinformatics Analysis and Experimental Verification

Abstract

The ability of blood transcriptome analysis to identify dysregulated pathways and outcome-related genes following myocardial infarction remains unknown. Two gene expression datasets (GSE60993 and GSE61144) were downloaded from Gene Expression Omnibus (GEO) Datasets to identify altered plasma transcriptomes in patients with ST-segment elevated myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. GEO2R, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes annotations, protein–protein interaction analysis, etc., were adopted to determine functional roles and regulatory networks of differentially expressed genes (DEGs). Dysregulated expressomes were verified at transcriptional and translational levels by analyzing the GSE49925 dataset and our own samples, respectively. A total of 91 DEGs were identified in the discovery phase, consisting of 15 downregulated genes and 76 upregulated genes. Two hub modules consisting of 12 hub genes were identified. In the verification phase, six of the 12 hub genes exhibited the same variation patterns at the transcriptional level in the GSE49925 dataset. Among them, S100A12 was shown to have the best discriminative performance for predicting in-hospital mortality and to be the only independent predictor of death during follow-up. Validation of 223 samples from our center showed that S100A12 protein level in plasma was significantly lower among patients who survived to discharge, but it was not an independent predictor of survival to discharge or recurrent major adverse cardiovascular events after discharge. In conclusion, the dysregulated expression of plasma S100A12 at the transcriptional level is a robust early prognostic factor in patients with STEMI, while the discrimination power of the protein level in plasma needs to be further verified by large-scale, prospective, international, multicenter studies.

Role of serum CAP1 protein in the diagnosis of patients with first-time acute myocardial infarction

“…The diagnostic accuracy of CAP1 in AMI was similar to that of heart-type fatty acid binding protein (H-FABP) and S100 calcium binding protein A12 (S100A12), but was lower than that of Cardiac myosin-binding protein C (cMyBP-C). [28][29][30] Moreover, CAP1 combined with cTnI has superior diagnostic value than CAP1 and cTnI alone, indicating the combination of CAP1 and cTnI as biomarkers in clinical practice is feasible and effective. In addition, the expression of CAP1 in participants of patients with first-time AMI was positively interrelated with ox-LDL level, and CAP1 expression was increased in ox-LDL induced HUVEC in a doseand time-dependent manner.…”

Identifying potential biomarkers in acute myocardial infarction based on neutrophil extracellular traps associated genes

“…Moreover, the AUC value of S100A12 was as high as 0.896, indicating its great potential as a diagnostic marker for AMI. Interestingly, several studies have also suggested that S100A12 could be a diagnostic biomarker for early AMI (40,41,42).…”

An integrated signature of clinical metrics and immune-related genes as a prognostic indicator for ST-segment elevation myocardial infarction patient survival

“…These datasets—namely GSE29111, GSE60993, GSE61144, GSE34198, GSE49925, and GSE34571—represented the most prevalent sample types. However, due to specific limitations [ 11 ], we excluded datasets GSE29111, GSE34198, and GSE34571. To facilitate our analysis, we selected three datasets (GSE49925 [ 12 ], GSE60993 [ 13 ], and GSE61144 [ 13 ]) for further investigation.…”

“…Our prior research has illuminated the prognostic significance of specific IRGs, including CD8A , IL2RB , and S100A12 , within the context of STEMI [ 11 ]. These findings underscore the potential of integrating clinical parameters with IRG profiles to construct a robust predictive model for patient outcomes.…”