Role of mitochondrial metabolism in immune checkpoint inhibitors-related myocarditis.
Role of mitochondrial metabolism in immune checkpoint inhibitors-related myocarditis.
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DOI：
10.3389/fcvm.2023.1112222
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发表时间：
2023
影响因子：
3.6
通讯作者：
Zou, Jianyong
中科院分区：
文献类型：
--
作者：
Zhang, Xin;Gan, Yi;Zhu, Haoshuai;Liu, Zhihao;Yao, Xiaojing;Cheng, Chao;Liu, Zhenguo;Su, Chunhua;Zou, Jianyong
免疫检查点相关心肌炎是免疫治疗最致命的并发症。然而，其发生和发展的病理生理机制仍不清楚。由于长期缺乏有效的早期诊断和治疗方案，了解免疫检查点通道相关心肌炎的病理生理机制具有重要意义。从三名免疫检查点相关心肌炎患者和三名对照组织样本中收集组织样本进行蛋白质分析。利用基于TMT标记的定量蛋白质组学技术筛选差异表达蛋白。蛋白质-蛋白质相互作用（PPI）和基因本体论（GO）功能富集分析的交叉因子，随后进行。结合PD-L1亚细胞器水平的蛋白质相互作用网络，我们寻找了免疫检查点通道相关心肌炎中涉及的枢纽蛋白，并探索了潜在的药物敏感性和疾病相关性。在免疫检查点通道相关心肌炎中共鉴定出306个差异表达蛋白。富集分析表明差异表达蛋白与线粒体代谢密切相关。通过分析RAPA相关蛋白和PD-L1相关蛋白，我们发现了4个中心蛋白，即哺乳动物雷帕霉素靶蛋白（mTOR）、糖原合成酶激酶3β（GSK 3 β）、蛋白酪氨酸磷酸酶非受体11型（PTPN 11）和线粒体融合蛋白2（MFN 2），表明它们与免疫检查点相关心肌炎密切相关。最后，我们探索了治疗免疫检查点通道相关心肌炎的潜在药物。线粒体代谢参与了免疫检查点通道相关心肌炎的过程，我们鉴定了四种枢纽蛋白，它们可能成为免疫检查点通道相关心肌炎早期诊断和治疗的新生物标志物。
Immune checkpoint inhibitor-related myocarditis is the deadliest complication of immunotherapy. However, the underlying pathophysiological mechanisms of its occurrence and development remain unclear. Due to the long-term lack of effective early diagnosis and treatment options, it is of great significance to understand the pathophysiological mechanism of immune checkpoint inhibitor-related myocarditis. Tissue samples from three patients with immune checkpoint inhibitor-related myocarditis and three control tissue samples were collected for protein analysis. Differentially expressed proteins were screened out using quantitative proteomics technology based on TMT markers. Protein–protein interaction (PPI) and Gene Ontology (GO) functional enrichment analyses of cross-factors were subsequently performed. Combined with the PD-L1 subcellular organelle- level protein interaction network, we searched for hub proteins involved in immune checkpoint inhibitor-related myocarditis and explored potential drug sensitivity and disease correlation. A total of 306 differentially expressed proteins were identified in immune checkpoint inhibitor-related myocarditis. Enrichment analysis showed that the differentially expressed proteins were closely related to mitochondrial metabolism. By analyzing mitochondria-related proteins and PD-L1-related proteins, we found four hub proteins, mammalian target of rapamycin (mTOR), Glycogen synthase kinase 3β (GSK3β), Protein tyrosine phosphatase non-receptor type 11 (PTPN11), and Mitofusin 2 (MFN2), indicating that they are closely related to immune checkpoint inhibitor-related myocarditis. Finally, we explored potential drugs for the treatment of immune checkpoint inhibitor-related myocarditis. Mitochondrial metabolism is involved in the process of immune checkpoint inhibitor-related myocarditis, and we identified four hub proteins, which may become new biomarkers for the early diagnosis and treatment of immune checkpoint inhibitor-related myocarditis.
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发表时间：
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期刊：
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影响因子：
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