Transcriptomic Analysis of Tight Junction Proteins Demonstrates the Aberrant Expression and Function of Zona Occludens 2 (ZO-2) Protein in Stanford Type A Aortic Dissection

Abstract

Objective: Thoracic aortic aneurysm dissection (TAAD) represents a cardiac surgery emergency characterized by the disrupted integrity of the aortic wall and is associated with poor prognosis. In this context, the identification of biomarkers implicated in the pathobiology of TAAD is crucial. Our aim in the present original in silico study is to assess the differential gene expression profile of the tight junction proteins (TJPs) in patients with TAAD and to propose novel biomarkers for the diagnosis and prognosis of this disease. Methods: We implemented bioinformatics methodology in order to construct the gene network of the TJPs family, identify the differentially expressed genes (DEGs) in pathologic aortic tissue excised from patients with TAAD as compared to healthy aortic tissue, and assess the related biological functions and the associated miRNA families. Results: Data regarding the transcriptomic profile of selected genes were retrieved and incorporated from three microarray datasets, including 23 TAAD and 20 healthy control samples. A total of 32 TJPs were assessed. The zona occludens 2 (ZO-2) protein encoded by the gene TJP2 was significantly under-expressed in patients with TAAD compared to the control group (p = 0.009). ZO-2 was associated with fair discrimination and calibration traits in predicting the TAAD presentation. CpG islands of ZO-2 were demonstrated. No important difference was found regarding ZO-2 expression between aneurysmal non-dissected and healthy control aortic tissue. Finally, we performed gene set enrichment analysis (GSEA) and uncovered the major biological functions and miRNA families (hsa-miR-155-5p, hsa-miR-1-3p, hsa-miR-2118-5p, hsa-miR-4691-3p, and hsa-miR-1229-3p) relevant to ZO-2. Conclusions: These outcomes demonstrated the important role of ZO-2 in the pathobiology of TAAD.