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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 and Lijun Zhang*   Pages 1 - 11 ( 11 )

Abstract:


Background: Moyamoya disease (MMD) is a rare cerebrovascular disease with high rate of disability and mortality. Immune reactions has 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 proteomic study.

Method: In this work, dural tissues or plasma from 98 patients with MMD, 17 disease control without MMD, and 12 healthy donors were collected. 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 MMD-related 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 are 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 has sex- and MMD Suzuki grade-dependence. Through receiver operating characteristic (ROC) analysis, HP can well discriminate MMD and healthy donors with area under the curve (AUC) of 0.953.

Conclusion: we identified a biggest protein database of the dura mater. 29 of 82 differentially expressed proteins in MMD are involved in 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, Biomarker

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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