Dataset Information

Differential proteomics-based identification by MALDI-MSMS and nLC-MSMS of biomarkers in serum of patients with glaucoma

ABSTRACT: Primary Open-Angle Glaucoma (POAG) and Pseudoexfoliation Glaucoma (PEXG) are forms of glaucoma with distinct etiologies, but they share a common type of optic neurodegeneration that leads to irreversible loss of retinal ganglion cells, visual field and blindness if left untreated. The main objective in the present study was to explore whether differential-proteomic analysis of blood serum from patients with POAG or PEXG could lead to the identification of candidate biomarkers of glaucoma and provide clues to pathogenic mechanisms. A total of 202 blood samples from medically treated patients with POAG (n=73), PEXG (n=59), and cataracts (control, n=70) were collected and analyzed following a proteomic workflow that involved two phases: discovery and validation. In the discovery phase, differential-proteomics (2D-DIGE) methodology led to the identification of a panel of 35 proteins that were altered (i.e., over- or under-expressed) in serum samples of glaucoma patients. Functional pathway analysis suggested a potential involvement of these proteins in immunological and inflammatory pathways. In the validation phase, ELISA assays of the top-17-ranked proteins confirmed that most of them were over-expressed in the glaucoma groups. Stepwise discriminant analysis of the ELISA data resulted in a six-protein panel (APOA4, TF, C3, APOL1, IGHG2, C4A) that was used to generate multivariate predictive models. These models achieved a diagnostic efficiency of 81% (correct assignment), specificity of 83%, and sensitivity of 92%. Specifically, 100% efficacy was reached in the discrimination of the POAG group from control, and 86% efficacy in the discrimination of POAG from PEXG. Overall, these data demonstrate the discovery of a panel of serum biomarkers that could be used in large-scale multiplexed screenings for the diagnosis of POAG and PEXG patients. Furthermore, these biomarkers may have a role in the pathogenesis, and association to immune-inflammatory processes with glaucoma.

INSTRUMENT(S): autoflex, LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Hector Gonzalez-Iglesias

PROVIDER: PXD000198 | Pride | 2014-01-17

REPOSITORIES: Pride

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Comparative proteomic study in serum of patients with primary open-angle glaucoma and pseudoexfoliation glaucoma.

González-Iglesias Héctor H Álvarez Lydia L García Montserrat M Escribano Julio J Rodríguez-Calvo Pedro Pablo PP Fernández-Vega Luis L Coca-Prados Miguel M

Journal of proteomics 20131216

Alterations in the sera proteins between patients with Primary Open-Angle Glaucoma (POAG), Pseudoexfoliation Glaucoma (PEXG), and healthy controls were identified through a proven approach utilizing equalization of high-abundance serum proteins with ProteoMiner™, two-dimensional fluorescent difference gel electrophoresis (2D-DIGE), MALDI-TOF/TOF, and nanoLC-MS-MS. Quantitative immunoassays of the 17 most-differentially-altered proteins identified in this analysis confirmed that they were also ov ...[more]

PMID: 24355480

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