title: Discovery and verification of urinary peptides in type 2 diabetes mellitus with kidney injury.
abstract: Varying degrees of renal injury could lead to different changes in urinary protein composition. We want to find urinary candidate peptide biomarkers in type 2 diabetic patients with different extents of kidney injury. Two sets of patients were recruited. Discovery set: weak cationic-exchange magnetic beads coupled with matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used to profile the low-molecular weight peptidome in urine samples from type 2 diabetes patients with normoalbuminura and microalbuminuria. The differently expressed urinary peptides were screened by ClinProTools2.1 bioinformatics software and identified through nano-liquid chromatography-tandem mass spectrometry. Verification set: the above screened urinary peptides were validated by use matrix-assisted laser desorption ionization time-of-flight mass spectrometry on another group of type 2 diabetes patients with different extents use of kidney injury. In the screening and identification stages, seven urinary peptides were selected as the most promising biomarker candidates, and they were identified as fragments of vitronectin precursor, isoform 1 of fibrinogen alpha chain precursor, prothrombin precursor and inter-alpha-trypsin inhibitor heavy chain H4. The diagnostic efficacy of these urinary peptides was evaluated by area under the receiver operating characteristic curve, and they were 0.767, 0.768, 0.868, 0.910, 0.860, 0.843, and 0.865, respectively. In the verification stage, m/z 1743.9, 2154, 2175.5, and 2184.9 were decreased as albumin-to-creatinine (Alb/Cre) increased and m/z 2231.1, 2430.8, and 2756.1 were elevated as Alb/Cre rose. These small molecule peptides are related to type 2 diabetes kidney damage, and they may play an important role in monitoring type 2 diabetes.
authors: Department of Clinical Laboratory, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Beijing 100038, China.
authors: Guangzhen
authors: G
authors: Fu
authors: Department of Nephrology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
authors: Ye
authors: Y
authors: Du
authors: Department of Clinical Laboratory, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Beijing 100038, China.
authors: Lina
authors: L
authors: Chu
authors: Department of Clinical Laboratory, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Beijing 100038, China Department of Clinical Laboratory, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics Beijing, China Chinese Medical Doctor Association of Lab Medicine, Beijing, China mzhang99@aliyun.com.
authors: Man
authors: M
authors: Zhang
mesh_terms: D015415:Biomarkers / Q000652:urine*; D002853:Chromatography, Liquid; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000473:pathology*; D006801:Humans; D011507:Proteinuria / Q000473:pathology*; D020543:Proteome / Q000032:analysis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D014556:Urine / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D020543:Proteome
keywords: Urinary peptides; diabetes nephropathy; magnetic bead processing; matrix-assisted laser desorption ionization time-of-flight mass spectrometry; type 2 diabetes mellitus