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潜在诊断生物标志物:6 个铜死亡和铁死亡相关基因与急性心肌梗死中的免疫浸润相关联。

Potential diagnostic biomarkers: 6 cuproptosis- and ferroptosis-related genes linking immune infiltration in acute myocardial infarction.

机构信息

Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, Hebei, China.

Hebei Key Laboratory of Heart and Metabolism, Shijiazhuang, 050000, Hebei, China.

出版信息

Genes Immun. 2023 Aug;24(4):159-170. doi: 10.1038/s41435-023-00209-8. Epub 2023 Jul 8.


DOI:10.1038/s41435-023-00209-8
PMID:37422588
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10435388/
Abstract

The current diagnostic biomarkers of acute myocardial infarction (AMI), troponins, lack specificity and exist as false positives in other non-cardiac diseases. Previous studies revealed that cuproptosis, ferroptosis, and immune infiltration are all involved in the development of AMI. We hypothesize that combining the analysis of cuproptosis, ferroptosis, and immune infiltration in AMI will help identify more precise diagnostic biomarkers. The results showed that a total of 19 cuproptosis- and ferroptosis-related genes (CFRGs) were differentially expressed between the healthy and AMI groups. Functional enrichment analysis showed that the differential CFRGs were mostly enriched in biological processes related to oxidative stress and the inflammatory response. The immune infiltration status analyzed by ssGSEA found elevated levels of macrophages, neutrophils, and CCR in AMI. Then, we screened 6 immune-related CFRGs (CXCL2, DDIT3, DUSP1, CDKN1A, TLR4, STAT3) to construct a nomogram for predicting AMI and validated it in the GSE109048 dataset. Moreover, we also identified 5 pivotal miRNAs and 10 candidate drugs that target the 6 feature genes. Finally, RT-qPCR analysis verified that all 6 feature genes were upregulated in both animals and patients. In conclusion, our study reveals the significance of immune-related CFRGs in AMI and provides new insights for AMI diagnosis and treatment.

摘要

目前用于诊断急性心肌梗死(AMI)的生物标志物肌钙蛋白特异性不足,在其他非心脏疾病中也存在假阳性。先前的研究表明,铜死亡、铁死亡和免疫浸润都与 AMI 的发生有关。我们假设对 AMI 中的铜死亡、铁死亡和免疫浸润进行分析,将有助于识别更精确的诊断生物标志物。结果表明,在健康组和 AMI 组之间,共有 19 个铜死亡和铁死亡相关基因(CFRGs)存在差异表达。功能富集分析表明,差异表达的 CFRGs 主要富集在与氧化应激和炎症反应相关的生物学过程中。ssGSEA 分析发现 AMI 中的巨噬细胞、中性粒细胞和 CCR 水平升高。然后,我们筛选了 6 个与免疫相关的 CFRGs(CXCL2、DDIT3、DUSP1、CDKN1A、TLR4、STAT3),构建了一个用于预测 AMI 的列线图,并在 GSE109048 数据集上进行了验证。此外,我们还鉴定了 5 个关键 miRNA 和 10 个针对 6 个特征基因的候选药物。最后,RT-qPCR 分析验证了这 6 个特征基因在动物和患者中均上调。总之,本研究揭示了免疫相关 CFRGs 在 AMI 中的意义,为 AMI 的诊断和治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/704c83180ef5/41435_2023_209_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/ec8dde07a151/41435_2023_209_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/9f62afd64b80/41435_2023_209_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/fb75fce0a997/41435_2023_209_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/a2d28ce7ebdc/41435_2023_209_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/388b652d8b72/41435_2023_209_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/eab50651cb37/41435_2023_209_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/122fbc125aad/41435_2023_209_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/704c83180ef5/41435_2023_209_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/ec8dde07a151/41435_2023_209_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/9f62afd64b80/41435_2023_209_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/fb75fce0a997/41435_2023_209_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/a2d28ce7ebdc/41435_2023_209_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/388b652d8b72/41435_2023_209_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/eab50651cb37/41435_2023_209_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/122fbc125aad/41435_2023_209_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7c4/10435388/704c83180ef5/41435_2023_209_Fig8_HTML.jpg

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[7]
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本文引用的文献

[1]
Identification of GLS as a cuproptosis-related diagnosis gene in acute myocardial infarction.

Front Cardiovasc Med. 2022-11-11

[2]
Expression pattern and diagnostic value of ferroptosis-related genes in acute myocardial infarction.

Front Cardiovasc Med. 2022-11-3

[3]
The Role of Inflammation in Cardiovascular Disease.

Int J Mol Sci. 2022-10-26

[4]
Effect of Curcumin on Attenuation of Liver Cirrhosis via Genes/Proteins and Pathways: A System Pharmacology Study.

Nutrients. 2022-10-17

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Neuroprotective Effect of miR-483-5p Against Cardiac Arrest-Induced Mitochondrial Dysfunction Mediated Through the TNFSF8/AMPK/JNK Signaling Pathway.

Cell Mol Neurobiol. 2023-7

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Restoration of miR-648 overcomes 5-FU-resistance through targeting ET-1 in gastric cancer cells in-vitro.

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Identification of an 11 immune-related gene signature as the novel biomarker for acute myocardial infarction diagnosis.

Genes Immun. 2022-11

[8]
Ferroptosis and Autophagy-Related Genes in the Pathogenesis of Ischemic Cardiomyopathy.

Front Cardiovasc Med. 2022-6-30

[9]
The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease.

Nat Rev Cardiol. 2023-1

[10]
Roles of Ferroptosis in Cardiovascular Diseases.

Front Cardiovasc Med. 2022-5-23

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