Dysregulated circulating SOCS3 and haptoglobin expression associated with stable coronary artery disease and acute coronary syndrome: An integrated study based on bioinformatics analysis and case–control validation

OBJECTIVE: To extensively use blood transcriptome analysis to identify potential diagnostic and therapeutic targets for cardiovascular diseases. METHODS: Two gene expression datasets (GSE59867 and GSE62646) were downloaded from GEO DataSets to identify altered blood transcriptomes in patients with ST-segment elevation myocardial infarction (STEMI) compared to stable coronary artery disease (CAD). Thereafter, several computational approaches were taken to determine functional roles and regulatory networks of differentially expressed genes (DEGs). Finally, the expression of dysregulated two hub genes–suppressor of cytokine signaling 3 (SOCS3) and haptoglobin (HP)–were validated in a case–control study. RESULTS: A total of 119 DEGs were identified in the discovery phase, consisting of 71 downregulated genes and 48 upregulated genes; two hub modules consisting of two hub genes–SOCS3 and HP–were identified. In the validation phase, both SOCS3 and HP were significantly downregulated in the stable CAD and acute coronary syndrome (ACS) patients when compared with healthy controls. Meanwhile, HP was significantly upregulated in STEMI patients when compared with stable CAD patients (p=0.041). Logistic regression analysis indicated that: downregulated expression of HP correlated with increased risk of CAD [odds ratio (OR)=0.52, 95% confidence interval (CI)=0.31~0.87, p=0.013]; and downregulated expression of SOCS3 correlated with increased risk of ACS (OR=0.66, 95% CI=0.46~0.94, p=0.023) when age, gender, history of hyperlipidemia, diabetes and hypertension were included as covariates. CONCLUSION: Future clarification of how SOCS3 and HP influence the pathogenesis of disease may pave the way for the development of novel diagnostic and therapeutic methods.