iTRAQ-based Quantitative Proteomic Analysis of Dural Tissues Reveals Upregulated Haptoglobin to be a Potential Biomarker of Moyamoya Disease

Author(s): Xiaojun Zhang, Lin Yin, Xiaofang Jia, Yujiao Zhang, Tiefu Liu, Lijun Zhang*

Journal Name: Current Proteomics

Volume 18 , Issue 1 , 2021

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Abstract:

Background: Moyamoya Disease (MMD) is a rare cerebrovascular disease with a high rate of disability and mortality. Immune reactions have been implicated in the pathogenesis of MMD, however, the underlying mechanism is still unclear.

Objective: To identify proteins related to MMD specially involved in the immunogenesis, we performed a proteomic study.

Methods: In this work, dural tissues or plasma from 98 patients with MMD, 17 disease controls without MMD, and 12 healthy donors were included. Proteomic profiles of dural tissues from 4 MMD and 4 disease controls were analyzed by an isobaric tag for relative and absolute quantitation (iTRAQ)- based proteomics. The immune-related proteins were explored by bioinformatics and the key MMDrelated proteins were verified by western blot, multiple reaction monitoring methods, enzyme-linked immunosorbent assay, and tissue microarray.

Results: 1,120 proteins were identified, and 82 MMD-related proteins were found with more than 1.5 fold difference compared with those in the control samples. Gene Ontology analysis showed that 29 proteins were immune-related. In particular, Haptoglobin (HP) was up-regulated in dural tissue and plasma of MMD samples compared to the controls, and its up-regulation was found to be sex- and MMD Suzuki grade dependent. Through Receiver Operating Characteristic (ROC) analysis, HP can well discriminate MMD and healthy donors with the Area Under the Curve (AUC) of 0.953.

Conclusion: We identified the biggest protein database of the dura mater. 29 out of 82 differentially expressed proteins in MMD are involved in the immune process. Of which, HP was up-regulated in dural tissue and plasma of MMD, with sex- and MMD Suzuki grade-dependence. HP might be a potential biomarker of MMD.

Keywords: Moyamoya disease, dura mater, proteomics, iTRAQ, haptoglobin, strokes.

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Article Details

VOLUME: 18
ISSUE: 1
Year: 2021
Published on: 02 February, 2021
Page: [27 - 37]
Pages: 11
DOI: 10.2174/1570164617666191210103652
Price: $25

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