Systematic biomarker discovery and coordinative validation for different primary nephrotic syndromes using gas chromatography-mass spectrometry

Jung Eun Lee, Yu Ho Lee, Se Yun Kim, Yang Gyun Kim, Ju Young Moon, Kyung Hwan Jeong, Tae Won Lee, Chun Gyoo Ihm, Sooah Kim, Kyoung Heon Kim, Dong Ki Kim, Yon Su Kim, Chan Duck Kim, Cheol Whee Park, Do Yup Lee, Sang Ho Lee

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The goal of this study is to identify systematic biomarker panel for primary nephrotic syndromes from urine samples by applying a non-target metabolite profiling, and to validate their utility in independent sampling and analysis by multiplex statistical approaches. Nephrotic syndrome (NS) is a nonspecific kidney disorder, which is mostly represented by minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous glomerulonephritis (MGN). Since urine metabolites may mirror disease-specific functional perturbations in kidney injury, we examined urine samples for distinctive metabolic changes to identify biomarkers for clinical applications. We developed unbiased multi-component covarianced models from a discovery set with 48 samples (12 healthy controls, 12 MCD, 12 FSGS, and 12 MGN). To extensively validate their diagnostic potential, new batch from 54 patients with primary NS were independently examined a year after. In the independent validation set, the model including citric acid, pyruvic acid, fructose, ethanolamine, and cysteine effectively discriminated each NS using receiver operating characteristic (ROC) analysis except MCD-MGN comparison; nonetheless an additional metabolite multi-composite greatly improved the discrimination power between MCD and MGN. Finally, we proposed the re-constructed metabolic network distinctively dysregulated by the different NSs that may deepen comprehensive understanding of the disease mechanistic, and help the enhanced identification of NS and therapeutic plans for future.

Original languageEnglish
Pages (from-to)105-115
Number of pages11
JournalJournal of Chromatography A
Volume1453
DOIs
Publication statusPublished - 2016 Jul 1

Keywords

  • Bioinformatics
  • Biomarker panel
  • Gas-chromatography time-of-flight mass spectrometry
  • Human urine
  • Metabolomics
  • Nephrotic syndrome

ASJC Scopus subject areas

  • Analytical Chemistry
  • Organic Chemistry
  • Biochemistry

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  • Cite this

    Lee, J. E., Lee, Y. H., Kim, S. Y., Kim, Y. G., Moon, J. Y., Jeong, K. H., Lee, T. W., Ihm, C. G., Kim, S., Kim, K. H., Kim, D. K., Kim, Y. S., Kim, C. D., Park, C. W., Lee, D. Y., & Lee, S. H. (2016). Systematic biomarker discovery and coordinative validation for different primary nephrotic syndromes using gas chromatography-mass spectrometry. Journal of Chromatography A, 1453, 105-115. https://doi.org/10.1016/j.chroma.2016.05.058