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In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice
Published on: November 22, 2017
Mitophagy related diagnostic biomarkers for coronary in-stent restenosis identified using machine learning and
Ming Shen1,2, Meixian Chen3, Yu Chen4
1Department of Cardiology, the 926th Hospital of the Joint Logistic Support Force of PLA, Affiliated Hospital of Kunming University of Science and Technology, Kaiyuan, 661600, Yunnan, China. Dr_shenming@163.com.
Insights
Researchers identified LRRK2 and ANKRD13A as key mitophagy-related biomarkers for in-stent restenosis (ISR), a complication of coronary artery disease treatment. These findings offer new avenues for early diagnosis and precision medicine approaches to improve treatment efficacy.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Genomics
Background:
- Percutaneous coronary intervention (PCI) with stent implantation is a primary treatment for coronary artery disease (CAD).
- In-stent restenosis (ISR) remains a significant limitation, reducing the long-term effectiveness of PCI.
- The role of mitophagy, essential for vascular health, in ISR pathogenesis is not well understood.
Purpose of the Study:
- To identify mitophagy-related biomarkers for ISR.
- To elucidate the molecular mechanisms underlying mitophagy's involvement in ISR.
- To explore potential therapeutic strategies for ISR.
Main Methods:
- Differential gene expression analysis identified 169 differentially expressed genes (DEGs).
- Intersection with mitophagy-related genes (MRGs) yielded 23 differentially expressed mitophagy-related genes (DEMRGs).
- Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning algorithms (Logistic-LASSO, RF, SVM-RFE) identified LRRK2 and ANKRD13A as key biomarkers.
Main Results:
- LRRK2 and ANKRD13A were identified as robust mitophagy-related biomarkers for ISR.
- A nomogram incorporating these genes demonstrated promising diagnostic accuracy for ISR.
- Gene Set Enrichment Analysis (GSEA) and immune infiltration analyses revealed associations between these biomarkers and immune/inflammatory responses in ISR.
Conclusions:
- LRRK2 and ANKRD13A are significant mitophagy-related biomarkers for ISR.
- These biomarkers are linked to immune and inflammatory processes in ISR.
- The study provides novel insights for early ISR diagnosis and personalized therapeutic interventions.
Abstract:
Percutaneous coronary intervention (PCI) combined with stent implantation is currently one of the most effective treatments for coronary artery disease (CAD). However, in-stent restenosis (ISR) significantly compromises its long-term efficacy. Mitophagy plays a crucial role in vascular homeostasis, yet its role in ISR remains unclear. This study aims to identify mitophagy-related biomarkers for ISR and explore their underlying molecular mechanisms. Through differential gene expression analysis between ISR and Control samples in the combined dataset, 169 differentially expressed genes (DEGs) were identified. Twenty-three differentially expressed mitophagy-related genes (DEMRGs) were identified by intersecting with mitophagy-related genes (MRGs) from the GeneCards, and functional enrichment analysis indicated their significant involvement in mitophagy-related biological processes. Using Weighted Gene Co-expression Network Analysis (WGCNA) and three machine learning algorithms (Logistic-LASSO, RF, and SVM-RFE), LRRK2, and ANKRD13A were identified as mitophagy-related biomarkers for ISR. The nomogram based on these two genes also exhibited promising diagnostic performance for ISR. Gene Set Enrichment Analysis (GSEA) as well as immune infiltration analyses showed that these two genes were closely associated with immune and inflammatory responses in ISR. Furthermore, potential small molecule compounds with therapeutic implications for ISR were predicted using the connectivity Map (cMAP) database. This study systematically investigated mitophagy-related biomarkers for ISR and their potential biological functions, providing new insights into early diagnosis and precision treatment strategies for ISR.

