Lipocalin 2 as a new biomarker for fetal lung hypoplasia in congenital diaphragmatic hernia.

BACKGROUND

Congenital diaphragmatic hernia (CDH) causes pulmonary hypoplasia, which are often fatal. We established a new biomarker for fetal lung hypoplasia in CDH.

METHODS

We collected newborn lung tissue specimens at E21 from normal and nitrofen-induced CDH rats (administered 100mg orally at E9) and performed a microarray analysis and real-time PCR (RT-PCR). Sixty-three human amniotic fluid (AF) samples, including samples from isolated CDH cases (n=33) and Cesarean section (CS) cases without fetal complications (controls) (n=30), were obtained. All AF samples were obtained at the time of CS, which was performed after 35-38 gestational weeks, from April 2007 to January 2016.

RESULTS

A microarray analysis and RT-PCR showed decreased gene expression levels of lipocalin 2 (LCN2) in the nitrofen-induced CDH lungs (p<0.05). We next examined the LCN2 levels in human AF samples using ELISA and the levels were significantly lower in the CDH cases than in controls (73.7ng/ml vs 163.8ng/ml; p<0.05). A significant positive correlation was observed between the amniotic LCN2 level and the observed/expected lung-to-head ratio (p<0.001).

CONCLUSIONS

LCN2 may be a potentially useful biomarker for lung hypoplasia in a rat and human CDH.