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Bioinformatics identification of mitochondrial dynamics-related potential biomarkers in kawasaki disease and
Tingting Hu1, Shaoyong Lin1, Rongrong Yang1
1Department of Cardiology, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China.
Background:
Kawasaki disease (KD) is a systemic vasculitis. Mitochondria was found to promote the activation of NLRP3 inflammatory vesicles, which have been shown to be a key driver of vascular disease. And there are few relevant reports of mitochondrial dynamic (MD) in KD. This study aimed to distinguish the potential biomarkers related to MD in KD and supply ideas for the intervention and treatment of KD. Currently, functional experimental verification in this field is lacking, and this study preliminarily explores their potential correlations through bioinformatics analysis.
Methods:
Differential expression analysis, machine learning, and expression validation were employed to identify potential biomarkers. Subsequently, analyses like enrichment analysis, immune infiltration analysis, and molecular regulatory network were applied to probe the underlying mechanisms of potential biomarkers.
Results:
RAP2C, DPM2, and DDX59 were identified as potential biomarkers associated with MD in KD and were mainly involved in inflammation-related pathways. Notably, 13 differential immune cells were gained in KD and control groups, 9 of which showed strong correlation with potential biomarkers, suggesting a relationship between potential biomarkers and the immune microenvironment in KD. For example, DPM2 had the positive relationship with CD8 T cells, while DDX59 had the negative relationship with CD8 T cells. Afterwards, molecular regulatory networks of potential biomarkers were constructed, specifically, they shared 5 common microRNAs (miRNAs) and 3 common transcription factors (TFs). Ultimately, potential biomarkers had 3 common targeting drugs [valproic acid, benzo(a)pyrene, and acetaminophen]; notably, benzo(a)pyrene was excluded due to carcinogenicity, which supplied the basis for targeting potential biomarkers to treat KD.
Conclusion:
The potential biomarkers (RAP2C, DPM2, and DDX59) related to MD in KD were acquired. These findings provide preliminary insights for future drug repurposing studies targeting KD and offer bioinformatic evidence for a potential link between mitochondrial dynamics and the immune microenvironment in KD.
Insights
This study identifies RAP2C, DPM2, and DDX59 as potential biomarkers for Kawasaki disease (KD) linked to mitochondrial dynamics. Findings suggest a connection between these biomarkers, the immune microenvironment, and potential therapeutic targets for KD.
Area of Science:
- Cardiovascular Research
- Immunology
- Mitochondrial Biology
Background:
- Kawasaki disease (KD) is a critical systemic vasculitis impacting children.
- Mitochondrial dynamics (MD) are implicated in NLRP3 inflammasome activation and vascular inflammation.
- Limited research exists on the role of MD in KD pathogenesis.
Purpose of the Study:
- To identify potential biomarkers associated with mitochondrial dynamics in Kawasaki disease.
- To explore the underlying mechanisms and immune microenvironment correlations of these biomarkers.
- To provide a basis for novel therapeutic strategies and drug repurposing for KD.
Main Methods:
- Bioinformatic analysis including differential expression, machine learning, and expression validation.
- Enrichment analysis, immune infiltration analysis, and molecular regulatory network construction.
- Identification of common microRNAs, transcription factors, and potential drug targets.
Main Results:
- RAP2C, DPM2, and DDX59 identified as potential biomarkers for MD in KD, linked to inflammation.
- Significant correlations found between biomarkers and 13 differential immune cells, highlighting immune microenvironment involvement.
- Established molecular networks revealed shared miRNAs and TFs, with potential drug candidates like valproic acid and acetaminophen identified.
Conclusions:
- Discovered novel potential biomarkers (RAP2C, DPM2, DDX59) related to mitochondrial dynamics in Kawasaki disease.
- Provided bioinformatic evidence for the interplay between MD and the immune microenvironment in KD.
- Generated preliminary insights for drug repurposing and targeted KD interventions.
