Journal
BMC NEPHROLOGY
Volume 19, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12882-018-1139-3
Keywords
IgA nephropathy; Urinary proteomics; Uygur; Biomarker
Categories
Funding
- National Basic Research Program of China [2013CB530805, 2014CBA02005]
- National Key Research and Development Program of China [2016 YFC 1306300]
- Key Basic Research Program of the Ministry of Science and Technology of China [2013FY114100]
- National Natural Science Foundation of China [30970650, 31200614, 31400669, 81371515, 81170665, 81560121]
- Science and Technology Yuanjiang Project of Xinjiang Uygur Autonomous Region [2013911114]
- CAMS Innovation Fund for Medical Sciences [2017-I2M-1-009]
- Biologic Medicine Information Center of China, National Scientifc Data Sharing Platform for Population and Health, CAMS special basic research fund for central public research institutes [2017PT310004]
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BackgroundIgA nephropathy (IgAN) is one of the most common forms of idiopathic glomerular diseases and might lead to end-stage kidney disease. Accurate and non-invasive biomarkers for early diagnosis are required for early intervention and consequent therapy for IgAN patients. Because variance in the disease incidence and predisposing genes of IgAN has been detected among different ethnicities, the ethnicity factor should be considered in IgAN biomarker discovery. The differences in the protein profiles and pathological mechanisms of IgAN in patients of Uygur ethnicity need to be clearly illustrated.MethodsIn this study, we used urinary proteomics to discover candidate biomarkers of IgAN in patients of Uygur ethnicity. The urinary proteins from Uygur normal control and Uygur IgAN patients were extracted and analyzed using 2D-LC-MS/MS and isobaric tags for relative and absolute quantitation (iTRAQ) analysis.ResultsA total of 277 proteins were found to be differentially represented in Uygur IgAN compared with the respective normal controls. The bioinformatics analysis revealed that the immune response, cell survival, and complement system were activated in Uygur IgAN. Many differentially expressed proteins were found to be related to nephropathy and kidney injuries. Four candidate biomarkers were validated by Western blot, and these results were consistent with the iTRAQ results. ICAM1, TIMP1, SERPINC1 and ADIPOQ were upregulated in Uygur IgAN. Bioinformatic analysis revealed that the increase of ICAM1 and TIMP1 might be caused by IgAN, but the increase of SERPINC1 and ADIPOQ might be caused by proteinuria. SERPINC1 and ICAM1 were identified as the candidate biomarkers with excellent area-under-the-curve (AUC) values (0.84) for distinguishing Uygur IgAN from normal controls.ConclusionsUsing urinary proteomic analysis, we identified several candidate biomarkers for IgAN in patients of Uygur ethnicity. These results will prove helpful for exploring the pathological mechanism of IgAN in patients of Uygur ethnicity and for developing better treatments for these patients.
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