Knowledge-Based Identification of Soluble Biomarkers: Hepatic Fibrosis in NAFLD as an Example
Date
2013-02-06
Authors
Page, Sandra
Birerdinc, Aybike
Estep, Michael
Stepanova, Maria
Afendy, Arian
Petricoin, Emanuel
Younossi, Zobair
Chandhoke, Vikas
Baranova, Ancha
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
Abstract
The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1) NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2) biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases.
Description
Keywords
Citation
Page S, Birerdinc A, Estep M, Stepanova M, Afendy A, et al. (2013) Knowledge-Based Identification of Soluble Biomarkers: Hepatic Fibrosis in NAFLD as an Example. PLoS ONE 8(2): e56009. doi:10.1371/journal.pone.0056009