用生物信息学的方法筛选急性心肌梗死早期诊断的潜在生物标记物

A Bioinformatics Approach to Screen Potential Biomarker for The Early Diagnosis of Acute Myocardial Infarction

目的本研究旨在探究差异表达基因(Differentially expressed genes,DEG),然后鉴别出急性心肌梗死(Acute myocardial infarction,AMI)关键基因,由此筛查出可用于这种研究早期诊断的心脏疾病潜在生物标记物。方法 AMI患者(GSE19339)的基因表达数据下载自基因表达汇编数据库。采用affy程序包预处理后,在samar程序包内通过微阵列显著性分析(Significance analysis of mycroarray,SAM)算法筛选DEG。然后使用DAVID(注释可视化和整合发现数据库软件,database for annotation visualization and integrated discovery software)在线工具进行DEG功能和通路富集分析。进而采用GENET-IC_ASSOCIATION_DB_DISEASE分析和blastp比对算法筛选出AMI的相关基因。最后,将这些新基因用于转录因子和蛋白-蛋白相互作用网络分析。结果在AMI患者与正常对照样本间共筛选出633个DEG,包括378个上调DEG和255个下调DEG。在AMI中发现了一种显著差异表达的新基因LCK(淋巴细胞特异性蛋白酪氨酸激酶,lymphocytespecific protein tyrosine kinase)。进一步分析显示LCK参与CXCL12(趋化因子(C-X-C基序)配体12,chemokine(C-X-Cmotif)ligand12)的表达调节,而LCK的表达则由不同的转录因子进行调节。结论这项研究中,我们对AMI的发病机制提出了新见解,并提出LCK是这种严重心脏疾病的一个引人注目的候选标记物。

Objective This study aimed to explore the differentially expressed genes （DEGs） and then identify the critical genes in AMI thus screening out potential biomarkers for the early diagnosis of this serious heart disease. Methods The gene expression data of AMl patients （GSE19339） were downloaded from gene expression omnibus database. After preprocessing with affy package, the DEGs were screened out by significance analysis of microarray （SAM） algorithm within samr package. Then function and pathway enrichment analyses of the DEGs were carried out using DAVID （database for annotation visualization and integrated discovery software） online tools. Further, the relevant genes of AMI were screened out with GENETICASSOCIATION DB DISEASE analysis and blastp alignment. Finally, the novel genes were subjected to transcription factor and protein protein interaction network analyses. Results A total of 633 DEGs, including 378 up-regulated and 255 down-regulated, were screened out between AMI patients and normal control samples. Among those genes, several important ones such asPPAR, CCL2, HMOXIand NPRlwere demonstrated to be related to AMI. Most importantly, a novel gene LCK（lymphocyte-specific protein tyrosine kinase） was significantly differentially expressed in AMI. Further analyses showed thatLCKwas involved in the expression regulation of CXCL 12（chemokine （C-X-C motif） ligand 12） and the expression of LCKcan be regulated by different transcription factors. Conclusion In this study, we provided a new insight into the mechanism of AMI and raisedLCKas an attractive marker candidate in the diagnosis of this serious heart disease.