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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Comparative Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1707912

Upregulated Haptoglobin in Classical Monocytes Serves as a Diagnostic and Immunological Biomarker in Myocardial Infarction: A Cross-Sectional Multi-Omics Study

Provisionally accepted
Hongchen  XuHongchen XuHuibin  PanHuibin PanChanjuan  MoChanjuan MoXueqi  GuoXueqi GuoLongfei  JiLongfei JiDanfei  ShiDanfei ShiBinyu  WangBinyu WangGuodong  LiGuodong LiYong  LIYong LI*
  • The First People's Hospital of Huzhou, Huzhou, China

The final, formatted version of the article will be published soon.

Background: Myocardial infarction (MI) is one of the leading causes of death worldwide. Finding reliable diagnostic biomarkers and gaining a deeper understanding of their role in the immune microenvironment is of great significance for improving clinical prognosis. Method: This study integrated multiple datasets from GEO (GSE141512, GSE95368, GSE269269) and TCGA data, and used various bioinformatics methods such as weighted gene co-expression network analysis (WGCNA), immune cell infiltration analysis, and single-cell RNA sequencing analysis to screen key genes related to the occurrence and development of myocardial infarction. We initially validated the results using a proteomic dataset (GSE95368) and clinical samples analyzed by qPCR. Critically, the dysregulation and diagnostic value of Haptoglobin (HP) were further confirmed in multiple independent external cohorts (GSE66360, and others.), solidifying its reliability as a biomarker. Result: The study found that Haptoglobin (HP) is a key gene significantly upregulated in myocardial infarction, and it exhibits high diagnostic value (AUC=0.833) in the proteomic dataset (GSE95368). Single-cell sequencing analysis showed that HP is significantly highly expresed in classical monocyte of MI patients, and this finding was validated by qPCR experiments in clinically collected classical monocytes samples (p<0.05). Functional enrichment analysis implicated HP in immune responses and ferroptosis. Conclusion: The HP gene is a potential diagnostic biomarker for myocardial infarction, and its specific high expression in classical monocytes implies a potential role in the pathological process of myocardial infarction by regulating the immune microenvironment. This study provides a new research direction for the diagnosis and immune-targeted therapy of myocardial infarction, and has important clinical translational value.

Keywords: Myocardial Infarction, WGCNA, immune microenvironment, single-cell RNAsequencing, ferroptosis, Exosomes

Received: 18 Sep 2025; Accepted: 14 Oct 2025.

Copyright: © 2025 Xu, Pan, Mo, Guo, Ji, Shi, Wang, Li and LI. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yong LI, a821182777@qq.com

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