Abstract
BACKGROUND: The implication of necroptosis in cardiovascular disease was already recognized. However, the molecular mechanism of necroptosis has not been extensively studied in coronary heart disease (CHD). METHODS: The differentially expressed genes (DEGs) between CHD and control samples were acquired in the GSE20681 dataset downloaded from the GEO database. Key necroptosis-related DEGs were captured and ascertained by bioinformatics analysis techniques, including weighted gene co-expression network analysis (WGCNA) and two machine learning algorithms, while single-gene gene set enrichment analysis (GSEA) revealed their molecular mechanisms. The diagnostic biomarkers were selected via receiver operating characteristic (ROC) analysis. Moreover, an analysis of immune elements infiltration degree was carried out. Authentication of pivotal gene expression at the mRNA level was investigated in vitro utilizing quantitative real-time PCR (qRT-PCR). RESULTS: A total of 94 DE-NRGs were recognized here, among which, FAM166B, NEFL, POLDIP3, PRSS37, and ZNF594 were authenticated as necroptosis-related biomarkers, and the linear regression model based on them presented an acceptable ability to different sample types. Following regulatory analysis, the ascertained biomarkers were markedly abundant in functions pertinent to blood circulation, calcium ion homeostasis, and the MAPK/cAMP/Ras signaling pathway. Single-sample GSEA exhibited that APC co-stimulation and CCR were more abundant, and aDCs and B cells were relatively scarce in CHD patients. Consistent findings from bioinformatics and qRT-PCR analyses confirmed the upregulation of NEFL and the downregulation of FAM166B, POLDIP3, and PRSS37 in CHD. CONCLUSION: Our current investigation identified 5 necroptosis-related genes that could be diagnostic markers for CHD and brought a novel comprehension of the latent molecular mechanisms of necroptosis in CHD.