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

[ Vol. 18 , Issue. 1 ]

Author(s):

Xiaojun Zhang, Lin Yin, Xiaofang Jia, Yujiao Zhang, Tiefu Liu and Lijun Zhang*   Pages 27 - 37 ( 11 )

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.

Affiliation:

The 85th Hospital of the Chinese People's Liberation Army, Shanghai 200052, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508



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