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.
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: hiro-t@med.nagoya-u.ac.jp.
Hiroyuki
H
Tsuda
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Tomomi
T
Kotani
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Tomoko
T
Nakano
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Kenji
K
Imai
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Shima
S
Hirako
Bell Research Center for Reproductive Health and Center, Nagoya, Japan.
Hua
H
Li
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Fumitaka
F
Kikkawa
D000015:Abnormalities, Multiple; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D005260:Female; D005333:Fetus / Q000002:abnormalities*; D065630:Hernias, Diaphragmatic, Congenital / Q000097:blood* / Q000139:chemically induced; D006801:Humans; D000071068:Lipocalin-2 / Q000097:blood* / Q000235:genetics; D008168:Lung / Q000002:abnormalities*; D008297:Male; D046228:Microarray Analysis; D010647:Phenyl Ethers / Q000008:administration & dosage; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
D015415:Biomarkers; D000071068:Lipocalin-2; D010647:Phenyl Ethers; C007350:nitrofen
Amniotic fluid; Congenital diaphragmatic hernia; Lipocalin-2; Lung hypoplasia; Observed/expected lung-to-head ratio