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基于公共和二代测序转录组数据的系统生物信息学分析:急性心肌梗死中免疫相关基因的诊断价值及潜在机制研究

Systematic Bioinformatics Analysis Based on Public and Second-Generation Sequencing Transcriptome Data: A Study on the Diagnostic Value and Potential Mechanisms of Immune-Related Genes in Acute Myocardial Infarction.

作者信息

Tan Xiaobing, Dai Qingli, Sun Huang, Jiang Wenqing, Lu Si, Wang Ruxian, Lv Meirong, Sun Xianfeng, Lv Naying, Dai Qingyuan

机构信息

Department of Center of Stomatology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.

Department of Ultrasound, Dali Bai Autonomous Prefecture People's Hospital, The Third Affiliated Hospital of Dali University, Dali, China.

出版信息

Front Cardiovasc Med. 2022 Apr 14;9:863248. doi: 10.3389/fcvm.2022.863248. eCollection 2022.

Abstract

UNLABELLED

Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases worldwide. Advances in genomics have provided new ideas for the development of novel molecular biomarkers of potential clinical value for AMI.

METHODS

Based on microarray data from a public database, differential analysis and functional enrichment analysis were performed to identify aberrantly expressed genes in AMI and their potential functions. CIBERSORT was used for immune landscape analysis. We also obtained whole blood samples of 3 patients with AMI and performed second-generation sequencing (SGS) analysis. Weighted gene co-expression network analysis (WGCNA) and cross-tabulation analysis identified AMI-related key genes. Receiver operating characteristic (ROC) curves were used to assess the diagnostic power of key genes. Single-gene gene set enrichment analysis (GSEA) revealed the molecular mechanisms of diagnostic indicators.

RESULTS

A total of 53 AMI-related DEGs from a public database were obtained and found to be involved in immune cell activation, immune response regulation, and cardiac developmental processes. CIBERSORT confirmed that the immune microenvironment was altered between AMI and normal samples. A total of 77 hub genes were identified by WGCNA, and 754 DEGs were obtained from own SGS data. Seven diagnostic indicators of AMI were obtained, namely GZMA, NKG7, TBX21, TGFBR3, SMAD7, KLRC4, and KLRD1. The single-gene GSEA suggested that the diagnostic indicators seemed to be closely implicated in cell cycle, immune response, cardiac developmental, and functional regulatory processes.

CONCLUSION

The present study provides new diagnostic indicators for AMI and further confirms the feasibility of the results of genome-wide gene expression analysis.

摘要

未标注

急性心肌梗死(AMI)是全球最严重的心血管疾病之一。基因组学的进展为开发具有潜在临床价值的新型急性心肌梗死分子生物标志物提供了新思路。

方法

基于公共数据库的微阵列数据,进行差异分析和功能富集分析,以识别急性心肌梗死中异常表达的基因及其潜在功能。使用CIBERSORT进行免疫景观分析。我们还获取了3例急性心肌梗死患者的全血样本,并进行了二代测序(SGS)分析。加权基因共表达网络分析(WGCNA)和交叉表分析确定了与急性心肌梗死相关的关键基因。采用受试者工作特征(ROC)曲线评估关键基因的诊断能力。单基因基因集富集分析(GSEA)揭示了诊断指标的分子机制。

结果

从公共数据库中获得了总共53个与急性心肌梗死相关的差异表达基因(DEG),发现它们参与免疫细胞激活、免疫反应调节和心脏发育过程。CIBERSORT证实急性心肌梗死和正常样本之间的免疫微环境发生了改变。通过WGCNA确定了总共77个枢纽基因,并从我们自己的SGS数据中获得了754个DEG。获得了7个急性心肌梗死的诊断指标,即颗粒酶A(GZMA)、自然杀伤细胞颗粒酶7(NKG7)、T盒转录因子21(TBX21)、转化生长因子β受体3(TGFBR3)、SMAD家族成员7(SMAD7)、杀伤细胞凝集素样受体亚家族C成员4(KLRC4)和杀伤细胞凝集素样受体亚家族D成员1(KLRD1)。单基因GSEA表明,这些诊断指标似乎与细胞周期、免疫反应、心脏发育和功能调节过程密切相关。

结论

本研究为急性心肌梗死提供了新的诊断指标,并进一步证实了全基因组基因表达分析结果的可行性。

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