SELDI-TOF-MS proteomic profiling of serum, urine, and amniotic fluid in neural tube defects.

Zhenjiang Liu,Qun Zhao,Zhengwei Yuan,Elizabeth J Coulson

doi:10.1371/journal.pone.0103276

Abstract

Neural tube defects (NTDs) are common birth defects, whose specific biomarkers are needed. The purpose of this pilot study is to determine whether protein profiling in NTD-mothers differ from normal controls using SELDI-TOF-MS. ProteinChip Biomarker System was used to evaluate 82 maternal serum samples, 78 urine samples and 76 amniotic fluid samples. The validity of classification tree was then challenged with a blind test set including another 20 NTD-mothers and 18 controls in serum samples, and another 19 NTD-mothers and 17 controls in urine samples, and another 20 NTD-mothers and 17 controls in amniotic fluid samples. Eight proteins detected in serum samples were up-regulated and four proteins were down-regulated in the NTD group. Four proteins detected in urine samples were up-regulated and one protein was down-regulated in the NTD group. Six proteins detected in amniotic fluid samples were up-regulated and one protein was down-regulated in the NTD group. The classification tree for serum samples separated NTDs from healthy individuals, achieving a sensitivity of 91% and a specificity of 97% in the training set, and achieving a sensitivity of 90% and a specificity of 97% and a positive predictive value of 95% in the test set. The classification tree for urine samples separated NTDs from controls, achieving a sensitivity of 95% and a specificity of 94% in the training set, and achieving a sensitivity of 89% and a specificity of 82% and a positive predictive value of 85% in the test set. The classification tree for amniotic fluid samples separated NTDs from controls, achieving a sensitivity of 93% and a specificity of 89% in the training set, and achieving a sensitivity of 90% and a specificity of 88% and a positive predictive value of 90% in the test set. These suggest that SELDI-TOF-MS is an additional method for NTDs pregnancies detection.

Highlights

The prevalence of neural tube defects (NTDs) is known to vary significantly based upon geography and ethnicity, with ranges from 0.5 to 6 in 1,000 newborns [1]
maternal serum alpha-fetoprotein (MSAFP), amniotic fluid alpha-1 fetoprotein (AFP) (AFAFP), and amniotic fluid cholinesterases are the primary protein biomarkers used in the prenatal diagnosis for NTDs [1]
MSAFP screening and ultrasonography are both used for prenatally detecting NTD-affected fetuses

Summary

Introduction

The prevalence of neural tube defects (NTDs) is known to vary significantly based upon geography and ethnicity, with ranges from 0.5 to 6 in 1,000 newborns [1]. There are multiple types of isolated NTDs including spina bifida and anencephaly [2]. It has been determined that in a fetus with an NTD, exposed membranes allow AFP to leak into the amniotic fluid and into maternal serum, at a level of roughly in proportion to the size of the exposed area. A matter of some controversy, when the spina bifida lesion is covered with healthy skin, MSAFP and amniotic fluid AFP (AFAFP) concentrations are generally found to be normal. Norem and coworkers found that among the 102 NTDs cases who had received MSAFP testing, 25 cases (25%) had negative maternal serum screening results, including 15 (38%) of the 40 spina bifida cases tested, 6 (67%) of the 9 encephalocele cases tested, and 4 (8%) of the 53 anencephaly cases [3]. Kooper et al found that 27 out of 6,188 pregnancies (0.4%) without any increased NTD risk had AFAFP levels .2.5 MoM (multiples of the median), two of which were associated with NTDs; two out of 258 pregnancies (0.8%) with an increased NTD risk had elevated AFAFP levels and were associated with affected pregnancies; and 44 of 55 pregnancies (80%) with clinically diagnosed fetal NTDs had an increased AFAFP levels [2]

Methods

Results

Conclusion