PDF(Pubmed)
Abstract：
UNASSIGNED: Ferroptosis, a crucial type of programmed cell death, is directly linked to various cardiac disorders. However, the contribution of ferroptosis-related genes (FRGs) to Takotsubo syndrome (TTS) has not been completely understood.
UNASSIGNED: The objective of this study was to investigate the relationship between the FRGs and TTS.
UNASSIGNED: TTS rat models were established by isoprenaline injection. Heart tissues were subsequently harvested for total RNA extraction and library construction. Transcriptome data wereobtained transcriptome data for TTS and FRGs from our laboratory, and sources such as the Ferroptosis Database (FerrDb) and the Gene Expression Omnibus Database (GEO). 57 differentially expressed FRGs (DE-FRGs) were discovered. The LASSO and SVM-RFE algorithms were employed to identify Enpp2, Pla2g6, Etv4, and Il1b as marker genes, and logistic regression was applied to construct a diagnostic model. The important genes were validated by real time PCR and the external dataset. Finally, the extent of immune infiltration was explored.
UNASSIGNED: Among the 57 genes, there were 36 up-regulated and 21 down-regulated genes that exhibited distinct expression patterns in the TTS and healthy control samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the enriched pathways were primarily associated with pathways of neurodegeneration-multiple disease, while Gene Ontology (GO) analysis revealed that these genes were primarily linked to cellular response to external stimuli, outer membrane functions, and ubiquitin protein ligase binding. After the identification of four marker genes as potentially effective biomarkers for TTS diagnosis, subsequent logistic regression modeling revealed a receiver operating characteristic curve (ROC) with an AUC of 1.0. The examination of immune cell infiltration showed significantly higher prevalence of activated CD4+ T cells, mast cells, etc., in TTS.
UNASSIGNED: Our findings support the theoretical importance of ferroptosis in TTS, highlighting Enpp2, Pla2g6, Etv4, and Il1b as potential diagnostic and therapeutic biomarkers for TTS.
UNASSIGNED: The objective of this study was to investigate the relationship between the FRGs and TTS.
UNASSIGNED: TTS rat models were established by isoprenaline injection. Heart tissues were subsequently harvested for total RNA extraction and library construction. Transcriptome data wereobtained transcriptome data for TTS and FRGs from our laboratory, and sources such as the Ferroptosis Database (FerrDb) and the Gene Expression Omnibus Database (GEO). 57 differentially expressed FRGs (DE-FRGs) were discovered. The LASSO and SVM-RFE algorithms were employed to identify Enpp2, Pla2g6, Etv4, and Il1b as marker genes, and logistic regression was applied to construct a diagnostic model. The important genes were validated by real time PCR and the external dataset. Finally, the extent of immune infiltration was explored.
UNASSIGNED: Among the 57 genes, there were 36 up-regulated and 21 down-regulated genes that exhibited distinct expression patterns in the TTS and healthy control samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the enriched pathways were primarily associated with pathways of neurodegeneration-multiple disease, while Gene Ontology (GO) analysis revealed that these genes were primarily linked to cellular response to external stimuli, outer membrane functions, and ubiquitin protein ligase binding. After the identification of four marker genes as potentially effective biomarkers for TTS diagnosis, subsequent logistic regression modeling revealed a receiver operating characteristic curve (ROC) with an AUC of 1.0. The examination of immune cell infiltration showed significantly higher prevalence of activated CD4+ T cells, mast cells, etc., in TTS.
UNASSIGNED: Our findings support the theoretical importance of ferroptosis in TTS, highlighting Enpp2, Pla2g6, Etv4, and Il1b as potential diagnostic and therapeutic biomarkers for TTS.
摘要：
■铁凋亡，一种至关重要的程序性细胞死亡，与各种心脏疾病直接相关。然而,铁凋亡相关基因（FRGs）对Takotsubo综合征（TTS）的贡献尚未完全了解。
■本研究的目的是调查FRGs和TTS之间的关系。
■通过注射异丙肾上腺素建立TTS大鼠模型。随后收获心脏组织用于总RNA提取和文库构建。转录组数据从我们的实验室获得了TTS和FRG的转录组数据，和来源，如铁细胞凋亡数据库（FerrDb）和基因表达综合数据库（GEO）。发现了57个差异表达的FRG(DE-FRG)。LASSO和SVM-RFE算法用于鉴定Enpp2，Pla2g6，Etv4和Il1b作为标记基因，并应用逻辑回归构建诊断模型。通过实时PCR和外部数据集验证了重要基因。最后,探讨了免疫浸润的程度。
■在57个基因中，在TTS和健康对照样本中,有36个上调基因和21个下调基因表现出不同的表达模式.京都基因和基因组百科全书（KEGG）分析表明，富集的途径主要与神经变性-多发性疾病的途径有关。而基因本体论（GO）分析显示，这些基因主要与细胞对外界刺激的反应有关，外膜功能，和泛素蛋白连接酶结合。在确定了四个标记基因作为TTS诊断的潜在有效生物标志物后，随后的逻辑回归模型显示受试者工作特征曲线(ROC),AUC为1.0.免疫细胞浸润检查显示活化的CD4+T细胞患病率明显增高，肥大细胞,等。,在TTS。
■我们的研究结果支持TTS中铁中毒的理论重要性，强调Enpp2、Pla2g6、Etv4和Il1b是TTS的潜在诊断和治疗生物标志物。
■本研究的目的是调查FRGs和TTS之间的关系。
■通过注射异丙肾上腺素建立TTS大鼠模型。随后收获心脏组织用于总RNA提取和文库构建。转录组数据从我们的实验室获得了TTS和FRG的转录组数据，和来源，如铁细胞凋亡数据库（FerrDb）和基因表达综合数据库（GEO）。发现了57个差异表达的FRG(DE-FRG)。LASSO和SVM-RFE算法用于鉴定Enpp2，Pla2g6，Etv4和Il1b作为标记基因，并应用逻辑回归构建诊断模型。通过实时PCR和外部数据集验证了重要基因。最后,探讨了免疫浸润的程度。
■在57个基因中，在TTS和健康对照样本中,有36个上调基因和21个下调基因表现出不同的表达模式.京都基因和基因组百科全书（KEGG）分析表明，富集的途径主要与神经变性-多发性疾病的途径有关。而基因本体论（GO）分析显示，这些基因主要与细胞对外界刺激的反应有关，外膜功能，和泛素蛋白连接酶结合。在确定了四个标记基因作为TTS诊断的潜在有效生物标志物后，随后的逻辑回归模型显示受试者工作特征曲线(ROC),AUC为1.0.免疫细胞浸润检查显示活化的CD4+T细胞患病率明显增高，肥大细胞,等。,在TTS。
■我们的研究结果支持TTS中铁中毒的理论重要性，强调Enpp2、Pla2g6、Etv4和Il1b是TTS的潜在诊断和治疗生物标志物。
