MP80-19 URINE PROTEOMIC ANALYSIS IN CYSTINURIC PATIENTS WITH RENAL STONES

Abstract

You have accessJournal of UrologyStone Disease: Evaluation II1 Apr 2015MP80-19 URINE PROTEOMIC ANALYSIS IN CYSTINURIC PATIENTS WITH RENAL STONES Larisa Kovacevic, Hong Lu, Yegappan Lakshmanan, Joseph A. Caruso, and David Goldfarb Larisa KovacevicLarisa Kovacevic More articles by this author , Hong LuHong Lu More articles by this author , Yegappan LakshmananYegappan Lakshmanan More articles by this author , Joseph A. CarusoJoseph A. Caruso More articles by this author , and David GoldfarbDavid Goldfarb More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2855AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The pathogenesis of cystinuric renal stones is not well understood. Using a proteomic approach, we aimed to assess (1) the differences in the function of urinary proteins between patients with cystinuria and renal stone (CYS), patients with renal stone and no cystinuria (RS), and healthy controls (HC); (2) the gender differences in the proteomic profile within CYS group;(3) the presence of diagnostic biomarkers for CYS. METHODS We compared urinary proteomes of 10 patients with CYS (35.7±10.6 years, 5 males), 10 age- and gender-matched patients with RS, and 10 age- and gender-matched HC, using liquid chromatography-mass spectrometry (LC-MS/MS). Proteins of interest were selected based on relative fold-differences in abundance compared to controls, and were expressed as ratios. The pathway analysis using Gene Ontology (GO) annotation was done on the top 10% of proteins that exhibited the more pronounced differences in abundance between the groups. These significantly expressed proteins were used to analyze the group differences for biological processes, cellular components, and molecular function. RESULTS Of the 2219 proteins identified by proteomic analysis, 146 proteins were up-regulated in CYS and 80 proteins were up-regulated in HC. GO analysis in CYS showed a significant number of peptides involved in signal transduction (68 in males and 80 in females), and cell-cell signaling (17 in males and 21 in females). However, the signaling pathway was different in CYS males (Peroxisome Proliferator-Activated Receptor, PPAR) than in CYS females (NOTCH3). Proteins involved in fibrosis were found predominantly in CYS males (Table). Inter-alpha-trypsin inhibitor (ITIH), paraoxonase (PON1) and ceruloplasmin (CP) were more abundant in male CYS than female CYS and their matched HC. CONCLUSIONS Patients with cystinuria and renal stones have a different urinary polypeptide profile compared to healthy controls. Fibrosis is more common in male CYS, and an aggressive approach may be warranted. Additionally, we identified ITIH and CP as potential diagnostic biomarkers and novel therapeutic targets in CYS. These unique proteins merit further investigation. Accession Number∗ Protein MW (kDa) No. of assigned peptides∗∗ No. of unique peptides∗∗ Sequence coverage CYS/HC CYS/HC (%)∗∗∗ ITIH2 Inter-alpha-trypsin inhibitor 106 100 100 43.5 PON1 Paraoxonase 40 41.22 40.67 58.9 CP Ceruloplasmin 122 26.8 26.5 80.6 VIME Vimentin 54 8.35 8.28 23.8 IGFBP-6 Insulin-like growth factor-binding protein 6 25 3.35 3.3 4.17 ACTG Actin 42 3.28 4.11 66.1 MMP9 Matrix metalloproteinase 9 78 3.13 3.09 15.9 VCAM Vascular cell adhesion protein 81 2.12 2.1 35.3 ∗ Human. ∗∗ Values presented as CYS/HC ratios in males. ∗∗∗ % of sequence that has been identified for each protein. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1026-e1027 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Larisa Kovacevic More articles by this author Hong Lu More articles by this author Yegappan Lakshmanan More articles by this author Joseph A. Caruso More articles by this author David Goldfarb More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...