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Lipocalin-2: A novel biomarker for lung hypoplasia in congenital diaphragmatic hernia fetus
( Yoshinori Moriyama ),( Hiroyuki Tsuda ),( Tomomi Kotani ),( Seiji Sumigama ),( Tomoko Nakano ),( Shima Hirako ),( Fumitaka Kikkawa ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-
Objective: Congenital diaphragmatic hernia (CDH) results in pulmonary hypoplasia and pulmonary hypertension, which are often fatal. In order to improve clinical care and counseling, reliable prenatal parameters predicting outcome of CDH fetus are urgently needed. Some prenatal predictors of outcome of CDH fetus have been reported, but they are focused mainly on the assessment of fetal lung volume, and a gold-standard parameter has not yet been established. The aim of this study is to establish an accurate predictive marker for fetal lung hypoplasia in CDH cases. Methods: Neonatal lung tissue was collected at E21 from normal and nitrofen-induced CDH rats (administered 100 mg orally at E9), and microarray analysis and real-time polymerase chain reaction (RT-PCR) were performed. Sixty-three human amniotic fluid samples of isolated CDH cases (n = 33) and scheduled Cesarean section (CS) without any fetal complication (controls) (n = 30) were obtained with signed informed consent. All amniotic fluid samples were obtained at CS performed at 35th to 38th weeks of gestation from April 2007 to January 2016. Results: Genes which showed significantly decreased expression in nitrofen-induced CDH lung were lipocalin-2 (9-fold) and GATA-2 (3.3-fold). In lipocalin-2, this result was confirmed by RT-PCR. Next, the lipocalin-2 level in human amniotic fluid was examined using ELISA, and it was significantly lower in CDH cases than in controls (73.7 ng/mL vs 163.8 ng/mL; p < 0.05). A significant positive correlation was observed between amniotic lipocalin- 2 level and lung area to head circumference ratio (p < 0.001, r<sup>2</sup> = 0.453). Conclusion: Our results suggest that gene expression level of lipocalin-2 was significantly decreased in hypoplastic lung in rats, and that amniotic lipocalin-2 level was significantly lower in CDH cases in human. Amniotic lipocalin- 2 can be a useful marker to predict the prognosis of fetal CDH.