Zhai Hu, Huang Lei, Gong Yijie, Liu Yingwu, Wang Yu, Liu Bojiang, Li Xiandong, Peng Chunyan, Li Tong
Department of Heart Center, The Tianjin Third Central Hospital, Tianjin, China.
Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.
Front Cardiovasc Med. 2022 Jun 1;9:874436. doi: 10.3389/fcvm.2022.874436. eCollection 2022.
The ability of blood transcriptome analysis to identify dysregulated pathways and outcome-related genes following myocardial infarction remains unknown. Two gene expression datasets (GSE60993 and GSE61144) were downloaded from Gene Expression Omnibus (GEO) Datasets to identify altered plasma transcriptomes in patients with ST-segment elevated myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. GEO2R, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes annotations, protein-protein interaction analysis, etc., were adopted to determine functional roles and regulatory networks of differentially expressed genes (DEGs). Dysregulated expressomes were verified at transcriptional and translational levels by analyzing the GSE49925 dataset and our own samples, respectively. A total of 91 DEGs were identified in the discovery phase, consisting of 15 downregulated genes and 76 upregulated genes. Two hub modules consisting of 12 hub genes were identified. In the verification phase, six of the 12 hub genes exhibited the same variation patterns at the transcriptional level in the GSE49925 dataset. Among them, S100A12 was shown to have the best discriminative performance for predicting in-hospital mortality and to be the only independent predictor of death during follow-up. Validation of 223 samples from our center showed that S100A12 protein level in plasma was significantly lower among patients who survived to discharge, but it was not an independent predictor of survival to discharge or recurrent major adverse cardiovascular events after discharge. In conclusion, the dysregulated expression of plasma S100A12 at the transcriptional level is a robust early prognostic factor in patients with STEMI, while the discrimination power of the protein level in plasma needs to be further verified by large-scale, prospective, international, multicenter studies.
血液转录组分析在心肌梗死后识别失调通路和预后相关基因的能力尚不清楚。从基因表达综合数据库（GEO）下载了两个基因表达数据集（GSE60993和GSE61144），以识别接受直接经皮冠状动脉介入治疗的ST段抬高型心肌梗死（STEMI）患者血浆转录组的变化。采用GEO2R、基因本体论/京都基因与基因组百科全书注释、蛋白质-蛋白质相互作用分析等方法来确定差异表达基因（DEG）的功能作用和调控网络。分别通过分析GSE49925数据集和我们自己的样本，在转录和翻译水平验证失调的表达组。在发现阶段共鉴定出91个DEG，包括15个下调基因和76个上调基因。鉴定出由12个枢纽基因组成的两个枢纽模块。在验证阶段，12个枢纽基因中的6个在GSE49925数据集中的转录水平表现出相同的变化模式。其中，S100A12在预测院内死亡率方面具有最佳的判别性能，并且是随访期间死亡的唯一独立预测因子。对我们中心的223个样本进行验证表明，出院存活患者血浆中的S100A12蛋白水平显著较低，但它不是出院存活或出院后复发性主要不良心血管事件的独立预测因子。总之，血浆S100A12在转录水平的失调表达是STEMI患者强有力的早期预后因素，而血浆蛋白水平的判别能力需要通过大规模、前瞻性、国际性、多中心研究进一步验证。
