Urine Protein Biomarkers for the Diagnosis and Prognosis of Necrotizing Enterocolitis in Infants

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• 作者：Karl G. Sylvester ; MD¹ ; ² ; ^{sylvester@stanford.edu" class="auth_mail} ; Xuefeng B. Ling ; PhD² ; Gigi Yuen-Gee Liu ; MD² ; ³ ; Zachary J. Kastenberg ; MD¹ ; ² ; Jun Ji ; MS ; MD² ; Zhongkai Hu ; BS² ; Shuaibin Wu ; PhD² ; Sihua Peng ; PhD² ; Fizan Abdullah ; MD ; PhD³ ; Mary L. Brandt ; MD⁴ ; Richard A. Ehrenkranz ; MD⁵ ; Mary Catherine Harris ; MD⁶ ; Timothy C. Lee ; MD⁴ ; B. Joyce Simpson ; RN ; MPH⁵ ; Corinna Bowers ; CAP⁷ ; R. Lawrence Moss ; MD⁷
• 关键词：A2ML1 ; Alpha-2-macroglobulin-like protein 1 ; CD14 ; Cluster of differentiation protein 14 ; CST3 ; Cystatin 3 ; ELISA ; Enzyme-linked immunosorbent assay ; FGA ; Fibrinogen alpha chain ; IL ; interleukin ; LCMS ; Liquid chromatography/mass spectrometry ; NEC ; Necrotizing enterocolitis ; PEDF ; Pigment epithelium-derived factor ; RET4 ; Retinol binding protein 4 ; ROC ; Receiver-operator characteristic ; VASN ; Vasolin
• 刊名：The Journal of Pediatrics
• 出版年：March, 2014
• 年：2014
• 卷：164
• 期：3
• 页码：607-612.e7
• 全文大小：1833 K

文摘

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Objectives

To test the hypothesis that an exploratory proteomics analysis of urine proteins with subsequent development of validated urine biomarker panels would produce molecular classifiers for both the diagnosis and prognosis of infants with necrotizing enterocolitis (NEC).

Study design

Urine samples were collected from 119 premature infants (85 NEC, 17 sepsis, 17 control) at the time of initial clinical concern for disease. The urine from 59 infants was used for candidate biomarker discovery by liquid chromatography/mass spectrometry. The remaining 60 samples were subject to enzyme-linked immunosorbent assay for quantitative biomarker validation.

Results

A panel of 7 biomarkers (alpha-2-macroglobulin-like protein 1, cluster of differentiation protein 14, cystatin 3, fibrinogen alpha chain, pigment epithelium-derived factor, retinol binding protein 4, and vasolin) was identified by liquid chromatography/mass spectrometry and subsequently validated by enzyme-linked immunosorbent assay. These proteins were consistently found to be either up- or down-regulated depending on the presence, absence, or severity of disease. Biomarker panel validation resulted in a receiver-operator characteristic area under the curve of 98.2% for NEC vs sepsis and an area under the curve of 98.4% for medical NEC vs surgical NEC.

Conclusions

We identified 7 urine proteins capable of providing highly accurate diagnostic and prognostic information for infants with suspected NEC. This work represents a novel approach to improving the efficiency with which we diagnose early NEC and identify those at risk for developing severe, or surgical, disease.