目的:胸主动脉瘤(TAA)的特征是主动脉扩张,如果不及早诊断和治疗,预后不良。在这种情况下,关于TAA诊断的生物标志物的鉴定,监测和预后至关重要。本研究的目的是研究TAA患者钙黏着蛋白5(CDH5或VE-Cadherin)基因网络的差异基因表达谱,提出新的生物标志物。
方法:使用计算机技术构建CDH5网络的相互作用组,与健康对照相比,鉴定TAA中的差异表达基因(DEGs),并揭示相关的分子功能和调节miRNA。
结果:包含一个微阵列数据集的转录组学数据,纳入43个TAA和43个对照样品。鉴定出8个DEGs;7个上调,1个下调。8个基因的分子特征(CDH5;降钙素受体样受体-CALCRL;激活素A受体样1型-ACVRL1,色氨酸-TRNA合成酶1-WARS;连接斑红蛋白-JUP,蛋白酪氨酸磷酸酶受体J-PTPRJ,嘌呤能受体P2X4-P2RX4,激酶插入域受体-KDR)被鉴定为与TAA相关的生物标志物。PTPRJ与预测TAA表现的出色辨别和校准相关。CDH5-CALCRL的表达呈正相关,CDH5-ACVRL1、CDH5-WARS和CDH5-PTPRJ。最后,基因集富集分析表明分子功能和miRNA家族(hsa-miR-296-5p,hsa-miR-6836-5p,hsa-miR-6132、hsa-miR-27a-5p和hsa-miR-6773-5p)与8种生物标志物有关。
结论:这些结果提出了与TAA相关的8基因分子组。
OBJECTIVE: Thoracic aortic aneurysm (TAA) is characterized by the dilation of the aorta and is associated with poor prognosis if not diagnosed and treated early. In this context, the identification of biomarkers regarding the TAA diagnosis, monitoring and prognosis is crucial. The purpose of the current
study was to investigate the differential gene expression profile of the
cadherin 5 (CDH5 or VE-
Cadherin) gene network in patients with TAA, to propose novel biomarkers.
METHODS: In silico techniques were used to construct the interactome of the CDH5 network, identify the differentially expressed genes (DEGs) in TAA as compared to healthy controls, and uncover the related molecular functions and the regulating miRNAs.
RESULTS: Transcriptomic data of one microarray dataset were included, incorporating 43 TAA and 43 control samples. Eight DEGs were identified; 7 were up-regulated and 1 was down-regulated. A molecular signature of 8 genes (CDH5; Calcitonin Receptor-Like Receptor-CALCRL; Activin A Receptor-Like Type 1-ACVRL1, Tryptophanyl-TRNA Synthetase 1-WARS; Junction Plakoglobin-JUP, Protein Tyrosine Phosphatase Receptor Type J-PTPRJ, Purinergic Receptor P2X 4-P2RX4, Kinase Insert Domain Receptor-KDR) were identified as biomarkers associated with TAA. PTPRJ was associated with excellent discrimination and calibration in predicting TAA presentation. Positive correlations were reported regarding the expression of CDH5-CALCRL, CDH5-ACVRL1, CDH5-WARS and CDH5-PTPRJ. Finally, gene set enrichment analysis indicated the molecular functions and miRNA families (hsa-miR-296-5p, hsa-miR-6836-5p, hsa-miR-6132, hsa-miR-27a-5p and hsa-miR-6773-5p) relevant to the 8 biomarkers.
CONCLUSIONS: These outcomes propose an 8-gene molecular panel associated with TAA.