深入研究胸主动脉瘤患者钙黏蛋白 5 相互作用组，揭示 8 个新的生物标志物。

In-depth bioinformatic study of the cadherin 5 interactome in patients with thoracic aortic aneurysm unveils 8 novel biomarkers.

机构信息

Division of Surgery and Interventional Science, Faculty of Medical Sciences, UCL, London, UK.

Department of Cardiothoracic Surgery, University of Thessaly, Biopolis, Larissa, Greece.

出版信息

Eur J Cardiothorac Surg. 2021 Dec 27;61(1):11-18. doi: 10.1093/ejcts/ezab338.

DOI:10.1093/ejcts/ezab338

PMID:34293135

Abstract

OBJECTIVES

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.

摘要

目的

胸主动脉瘤（TAA）的特征是主动脉扩张，如果不能早期诊断和治疗，预后不佳。在这种情况下，鉴定与 TAA 诊断、监测和预后相关的生物标志物至关重要。本研究的目的是研究黏附素 5（CDH5 或 VE-钙粘蛋白）基因网络的差异基因表达谱，以提出新的生物标志物。

方法

使用计算机技术构建 CDH5 网络的互作组，鉴定 TAA 与健康对照相比的差异表达基因（DEGs），并揭示相关的分子功能和调节 miRNA。

结果

纳入了一个微阵列数据集的转录组数据，其中包含 43 个 TAA 和 43 个对照样本。鉴定出 8 个差异表达基因；其中 7 个上调，1 个下调。鉴定出 8 个基因（CDH5；降钙素受体样受体-CALCRL；激活素 A 受体样 1-ACVRL1，色氨酰 tRNA 合成酶 1-WARS；连接斑蛋白-JUP，蛋白酪氨酸磷酸酶受体 J 型-PTPRJ，嘌呤能受体 P2X4-P2RX4，激酶插入结构域受体-KDR）的分子特征作为与 TAA 相关的生物标志物。PTPRJ 与预测 TAA 表现的出色区分和校准相关。报道了 CDH5-CALCRL、CDH5-ACVRL1、CDH5-WARS 和 CDH5-PTPRJ 的表达之间存在正相关。最后，基因集富集分析表明与 8 个生物标志物相关的分子功能和 miRNA 家族（hsa-miR-296-5p、hsa-miR-6836-5p、hsa-miR-6132、hsa-miR-27a-5p 和 hsa-miR-6773-5p）。