Identification Novel Biomarker for Acute Aortic Dissection Using 4D-Label-Free Proteomics

Abstract

Purpose: we aimed to identify potential candidate biomarkers in aorta tissue from AAD patients. Methods: We used 4D label-free quantification (4D-LFQ) mass spectrometry to screen differentially expressed proteins in aorta tissues of AAD patients. Then we performed protein annotation, unsupervised hierarchical clustering, functional classification, functional enrichment and cluster, and protein-protein interaction analyses. Parallel Reaction Monitoring (PRM) technology was used to accurately and quantitatively confirm the selected target proteins. Results: A total of 3350 proteins were identified. Taking 1.5 times as the differential expression threshold, 139 were upregulated and 108 were downregulated as compared to the control groups. Bioinformatics analysis showed that the differential proteins were mainly distributed in extracellular matrix and cytoplasm. And their functions mainly involve cell migration and proliferation, inflammatory cell activation, cell contraction, muscle organ development and other processes. PRM technology accurately quantified the selected 20 target proteins, and found SAA1, LBP, MPO, and ENG were confirmed to be enriched in the aorta tissue of AAD patients. Conclusions: This is the first application of a 4D-LFQ-PRM workflow to identify and validate biomarkers in AAD patients. SAA1, LBP, MPO, and ENG represent novel biomarkers for the pathogenesis of AAD and might be a therapeutic target in the future.

Applying multi-omics techniques to the discovery of biomarkers for acute aortic dissection

“…Similar to the enrichment findings from transcriptomic analysis, the majority of the differentially expressed proteins for proteins outside of cells showed functions primarily involved in cell migration and proliferation, inflammatory cell activation, cell contraction, oxidative stress, and muscle organ development (130). Extracellular superoxide dismutase, an enzyme involved in oxidative stress, was one of them.…”

“…The integrin family functions as cell adhesion molecules that mediate cell-extracellular matrix attachment. As biomarkers for the diagnosis of AAD, they include reduced expression of integrin α-3 (ITGA-3), integrin α-5 (ITGA-5) (22), and high expression of integrin α-IIb (ITGA2B), integrin α-M (ITGAM), integrin β-2 (ITGB2), and integrin β-3 (ITGB3) (130). Meanwhile, MMP-9, a key enzyme involved in the breakdown of extracellular matrix and the migration of inflammatory cells, was discovered to be enhanced by integrins in immortalized keratin-forming cells and its inhibitors were able to reduce the incidence of AAD by 40% (131).…”