是什么增强了曲妥珠单抗的心脏毒性?通过对心肌细胞的综合回顾和 Meta 分析解码线粒体相关基因表达。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-03-01 Epub Date: 2024-03-11 DOI:10.1089/omi.2024.0004
Karoline Dos Santos Rodrigues, Daniel Sturza Lucas Caetano, João Vitor Cavalcante, Rodrigo Dalmolin, Patrícia K Ziegelmann, Michael Andrades
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引用次数: 0

摘要

曲妥珠单抗是一种单克隆抗体,用于治疗 HER2 阳性肿瘤。然而,作为一种不良反应,曲妥珠单抗会增加心力衰竭的风险,这意味着能量产生和线粒体过程参与其中。过去的研究通过转录组分析深入了解了与曲妥珠单抗安全性和毒性相关的通路,但有限的研究规模阻碍了最终结论的得出。因此,我们对曲妥珠单抗处理过的心肌细胞中线粒体相关基因表达数据进行了元分析。我们在 ArrayExpress、DDBJ Omics Archive、Gene Expression Omnibus、Google Scholar、PubMed 和 Web of Science 资源库中搜索了曲妥珠单抗处理的心肌细胞的转录组数据库。从《京都基因组百科全书》(Kyoto Encyclopedia of Genes and Genomes)和《基因本体资源》(Gene Ontology Resource)数据库中选择了与线粒体功能(生物发生、组织、丝裂噬和自噬)相关的 1270 个基因子集,使用 Metagen 软件包进行了本项荟萃分析(PROSPERO 的研究注册号:CRD42021270645)。三个数据集符合纳入标准,共对 1243 个基因进行了荟萃分析。我们观察到在曲妥珠单抗治疗后有69个基因上调,主要与自噬(28个基因)和线粒体组织(28个基因)有关。我们还发现了 37 个下调基因,主要与线粒体生物发生(11 个基因)和线粒体组织(24 个基因)有关。本荟萃分析表明,曲妥珠单抗疗法会导致线粒体功能失衡,这在一定程度上有助于解释心衰的发生,并产生了潜在的分子靶点列表。这些发现有助于我们了解曲妥珠单抗心脏毒性效应的分子机制,并可能对开发靶向疗法以减轻此类效应产生影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
What Powers Trastuzumab's Cardiotoxicity? Decoding Mitochondrial-Related Gene Expression Through Integrative Review and Meta-Analysis in Cardiomyocytes.

Trastuzumab is a monoclonal antibody used in oncotherapy for HER2-positive tumors. However, as an adverse effect, trastuzumab elevates the risk of heart failure, implying the involvement of energy production and mitochondrial processes. Past studies with transcriptome analysis have offered insights on pathways related to trastuzumab safety and toxicity but limited study sizes hinder conclusive findings. Therefore, we meta-analyzed mitochondria-related gene expression data in trastuzumab-treated cardiomyocytes. We searched the transcriptome databases for trastuzumab-treated cardiomyocytes in the ArrayExpress, DDBJ Omics Archive, Gene Expression Omnibus, Google Scholar, PubMed, and Web of Science repositories. A subset of 1270 genes related to mitochondrial functions (biogenesis, organization, mitophagy, and autophagy) was selected from the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology Resource databases to conduct the present meta-analysis using the Metagen package (Study register at PROSPERO: CRD42021270645). Three datasets met the inclusion criteria and 1243 genes were meta-analyzed. We observed 69 upregulated genes after trastuzumab treatment which were related mainly to autophagy (28 genes) and mitochondrial organization (28 genes). We also found 37 downregulated genes which were related mainly to mitochondrial biogenesis (11 genes) and mitochondrial organization (24 genes). The present meta-analysis indicates that trastuzumab therapy causes an unbalance in mitochondrial functions, which could, in part, help explain the development of heart failure and yields a list of potential molecular targets. These findings contribute to our understanding of the molecular mechanisms underlying the cardiotoxic effects of trastuzumab and may have implications for the development of targeted therapies to mitigate such effects.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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