Identification of PANoptosis-related hub genes in acute myocardial infarction: diagnostic potential, immune correlates, and therapeutic insights
摘要
PANoptosis is an innate immune-inflammatory programmed cell death pathway that integrates the key features of apoptosis, pyroptosis, and necroptosis. However, the diagnostic potential and immune relevance of PANoptosis-related genes in acute myocardial infarction (AMI) remain unclear.
MethodsTranscriptional data were obtained from the GEO database, including the training set GSE66360 and validation set GSE59867. Differential expression, protein-protein interaction networks, and random forest analyses were conducted to identify PANoptosis-related hub genes associated with AMI pathogenesis. The diagnostic model and nomogram were built, and the diagnostic value was evaluated using receiver operating characteristic analysis. Immune infiltration, functional enrichment, and regulatory network analyses were performed to explore potential molecular mechanisms. Blood samples from healthy controls and AMI patients were collected to validate the expression of hub genes.
ResultsA total of 438 DEGs and 109 PANoptosis-related genes were obtained. After intersecting these, 8 PANoptosis genes associated with AMI were found, enriched in apoptosis, immune, and inflammatory pathways. Two hub genes, IL1B and NLRP3, were identified as hub genes, with diagnostic models and nomograms showing good performance in both training and validation sets. These genes were significantly correlated with most immune cells that were dysregulated in AMI, revealing their immunomodulatory function. CEBPB and SPI1 were identified as common transcriptional regulators of the hub genes. Five drugs associated with hub genes were predicted from the DSigDB database. IL1B and NLRP3 showed consistent expression patterns across the training set, validation set, and real-time qPCR analysis.
ConclusionIL1B and NLRP3 may serve as PANoptosis-related biomarkers with potential immunomodulation in AMI, offering preliminary insights into the potential molecular mechanisms of PANoptosis in AMI.
Trial registrationNot applicable.