Identification and validation of ANXA3 and SOCS3 as biomarkers for acute myocardial infarction related to sphingolipid metabolism

Abstract Background Sphingolipid metabolism (SM) is linked to acute myocardial infarction (AMI), but its role remains unclear. This study explored SM-related genes (SMRGs) in AMI to support clinical diagnosis. Methods We analyzed datasets GSE48060 and GSE123342 to identify differentially expressed g...

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Main Authors: Ling Sun, Lingyan He, Hai-Hua Pan, Chang-Lin Zhai
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Hereditas
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Online Access:https://doi.org/10.1186/s41065-025-00515-3
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author Ling Sun
Lingyan He
Hai-Hua Pan
Chang-Lin Zhai
author_facet Ling Sun
Lingyan He
Hai-Hua Pan
Chang-Lin Zhai
author_sort Ling Sun
collection DOAJ
description Abstract Background Sphingolipid metabolism (SM) is linked to acute myocardial infarction (AMI), but its role remains unclear. This study explored SM-related genes (SMRGs) in AMI to support clinical diagnosis. Methods We analyzed datasets GSE48060 and GSE123342 to identify differentially expressed genes (DEGs) and key module genes. Protein-protein interaction (PPI) network analysis and machine learning were used to screen potential biomarkers, which were validated via receiver operating characteristic (ROC) curves and expression assessment. Further analyses included artificial neural networks (ANN), enrichment analysis, immune infiltration, drug prediction, and molecular docking. Single-cell RNA sequencing (scRNA-seq) identified key cell types and their functions. Biomarkers were validated via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results Intersection of 95 DEGs and 2,196 module genes yielded 20 genes, with ANXA3 and SOCS3 identified as biomarkers. The ANN model showed superior diagnostic performance compared to individual markers. Biomarkers were enriched in the toll-like receptor (TLR) signaling pathway. Immune infiltration analysis revealed differences in five immune cell types between AMI and control groups. ANXA3 correlated positively with neutrophils and negatively with resting memory CD4 T cells. Drugs targeting ANXA3 included ethanolamine, difluocortolone, and fluocinolone acetonide, with strong binding affinity. scRNA-seq identified B cells and monocytes as key cells; ANXA3 and SOCS3 expression increased during monocyte differentiation before decreasing, while B cells showed no significant changes. Conclusion ANXA3 and SOCS3 were identified as SM-related biomarkers in AMI, providing insights for clinical diagnosis.
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spelling doaj-art-dce5ea7d9ec34dbbbcae513b91c73a382025-08-20T03:43:27ZengBMCHereditas1601-52232025-08-01162112110.1186/s41065-025-00515-3Identification and validation of ANXA3 and SOCS3 as biomarkers for acute myocardial infarction related to sphingolipid metabolismLing Sun0Lingyan He1Hai-Hua Pan2Chang-Lin Zhai3Zhejiang Chinese Medical UniversityZhejiang Chinese Medical UniversityDepartment of Cardiology, The First Hospital of Jiaxing Affiliated Hospital of Jiaxing UniversityZhejiang Chinese Medical UniversityAbstract Background Sphingolipid metabolism (SM) is linked to acute myocardial infarction (AMI), but its role remains unclear. This study explored SM-related genes (SMRGs) in AMI to support clinical diagnosis. Methods We analyzed datasets GSE48060 and GSE123342 to identify differentially expressed genes (DEGs) and key module genes. Protein-protein interaction (PPI) network analysis and machine learning were used to screen potential biomarkers, which were validated via receiver operating characteristic (ROC) curves and expression assessment. Further analyses included artificial neural networks (ANN), enrichment analysis, immune infiltration, drug prediction, and molecular docking. Single-cell RNA sequencing (scRNA-seq) identified key cell types and their functions. Biomarkers were validated via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results Intersection of 95 DEGs and 2,196 module genes yielded 20 genes, with ANXA3 and SOCS3 identified as biomarkers. The ANN model showed superior diagnostic performance compared to individual markers. Biomarkers were enriched in the toll-like receptor (TLR) signaling pathway. Immune infiltration analysis revealed differences in five immune cell types between AMI and control groups. ANXA3 correlated positively with neutrophils and negatively with resting memory CD4 T cells. Drugs targeting ANXA3 included ethanolamine, difluocortolone, and fluocinolone acetonide, with strong binding affinity. scRNA-seq identified B cells and monocytes as key cells; ANXA3 and SOCS3 expression increased during monocyte differentiation before decreasing, while B cells showed no significant changes. Conclusion ANXA3 and SOCS3 were identified as SM-related biomarkers in AMI, providing insights for clinical diagnosis.https://doi.org/10.1186/s41065-025-00515-3Acute myocardial infarctionSphingolipid metabolismMachine learningImmune microenvironmentSingle cell RNA analysis
spellingShingle Ling Sun
Lingyan He
Hai-Hua Pan
Chang-Lin Zhai
Identification and validation of ANXA3 and SOCS3 as biomarkers for acute myocardial infarction related to sphingolipid metabolism
Hereditas
Acute myocardial infarction
Sphingolipid metabolism
Machine learning
Immune microenvironment
Single cell RNA analysis
title Identification and validation of ANXA3 and SOCS3 as biomarkers for acute myocardial infarction related to sphingolipid metabolism
title_full Identification and validation of ANXA3 and SOCS3 as biomarkers for acute myocardial infarction related to sphingolipid metabolism
title_fullStr Identification and validation of ANXA3 and SOCS3 as biomarkers for acute myocardial infarction related to sphingolipid metabolism
title_full_unstemmed Identification and validation of ANXA3 and SOCS3 as biomarkers for acute myocardial infarction related to sphingolipid metabolism
title_short Identification and validation of ANXA3 and SOCS3 as biomarkers for acute myocardial infarction related to sphingolipid metabolism
title_sort identification and validation of anxa3 and socs3 as biomarkers for acute myocardial infarction related to sphingolipid metabolism
topic Acute myocardial infarction
Sphingolipid metabolism
Machine learning
Immune microenvironment
Single cell RNA analysis
url https://doi.org/10.1186/s41065-025-00515-3
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