Adipocytokine Pathway Dysregulation Characterizes Immune-Related Molecular Subtypes and Candidate Biomarkers in...

Myocardial infarction (MI) is a critical cardiovascular event with a complex pathophysiology. This study aimed to investigate the role of the adipocytokine signaling pathway in MI, assess its potential association with diagnostic features, and explore its association with molecular subtypes.

Gene expression profiles from the GSE48060 and GSE66360 datasets were normalized and merged. Pathway activity was quantified using single-sample Gene Set Enrichment Analysis (ssGSEA). To prioritize genes of interest, we applied a machine learning approach using the XGBoost algorithm alongside multivariate logistic regression. Consensus clustering was then performed to explore MI subtypes, which were subsequently characterized by functional enrichment and immune cell infiltration analyses. In a small clinical cohort (n=6 per group), the expression levels of the prioritized genes were examined using qRT-PCR.

The adipocytokine pathway was significantly activated in MI samples compared to controls. By integrating XGBoost and logistic regression analyses, two common genes-IRS2 and SOCS3-were identified as promising candidates for further study. Consensus clustering based on pathway-related genes distinguished two distinct MI subtypes (C1 and C2). Notably, the C2 subtype exhibited higher adipocytokine pathway activity and greater infiltration of immune cells. Functional enrichment analysis revealed that the differentially expressed genes between subtypes were primarily associated with immune response and infectious disease pathways. qRT-PCR testing confirmed that IRS2 and SOCS3 were significantly differentially expressed in this cohort.

This study highlights IRS2 and SOCS3 as genes of interest within the adipocytokine pathway in MI. The identification of two distinct molecular subtypes with different pathway activity and immune landscapes provides a foundation for understanding MI heterogeneity and may generate hypotheses for future therapeutic stratification.