Zhang Xin, Gan Yi, Zhu Haoshuai, Liu Zhihao, Yao Xiaojing, Cheng Chao, Liu Zhenguo, Su Chunhua, Zou Jianyong
Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Front Cardiovasc Med. 2023 Jan 24;10:1112222. doi: 10.3389/fcvm.2023.1112222. eCollection 2023.
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.
免疫检查点抑制剂相关心肌炎是免疫治疗最致命的并发症。然而，其发生发展的潜在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法，了解免疫检查点抑制剂相关心肌炎的病理生理机制具有重要意义。
收集3例免疫检查点抑制剂相关心肌炎患者的组织样本和3例对照组织样本进行蛋白质分析。基于TMT标记物，采用定量蛋白质组学技术筛选差异表达蛋白。随后对交叉因子进行蛋白质-蛋白质相互作用（PPI）和基因本体（GO）功能富集分析。结合PD-L1亚细胞器水平的蛋白质相互作用网络，寻找参与免疫检查点抑制剂相关心肌炎的枢纽蛋白，并探索潜在的药物敏感性和疾病相关性。
在免疫检查点抑制剂相关心肌炎中总共鉴定出306种差异表达蛋白。富集分析表明，差异表达蛋白与线粒体代谢密切相关。通过分析线粒体相关蛋白和PD-L1相关蛋白，我们发现了4种枢纽蛋白，即雷帕霉素靶蛋白（mTOR）、糖原合酶激酶3β（GSK3β）、蛋白酪氨酸磷酸酶非受体11型（PTPN11）和线粒体融合蛋白2（MFN2），表明它们与免疫检查点抑制剂相关心肌炎密切相关。最后，我们探索了治疗免疫检查点抑制剂相关心肌炎的潜在药物。
线粒体代谢参与免疫检查点抑制剂相关心肌炎的发生过程，我们鉴定出4种枢纽蛋白，它们可能成为免疫检查点抑制剂相关心肌炎早期诊断和治疗的新生物标志物。
