Network analyses of differentially expressed proteins in amniotic fluid supernatant associated with abnormal human karyotypes.
OBJECTIVE
To investigate the functional roles of differentially expressed proteins in the amniotic fluid supernatant (AFS) with abnormal karyotypes.


METHODS
Basic and clinical research.


METHODS
University hospital.


METHODS
Samples of AFS from 34 fetuses with normal-karyotype, 17 with trisomy 18, and 19 with trisomy 21.


METHODS
Two-dimensional chromatography followed by mass spectrometry to identify the proteins differentially expressed in AFS of trisomy-18 or trisomy-21 fetuses.


METHODS
Differentially expressed proteins were confirmed with Western blot analysis and ELISA. The roles of biologic networks in the pathophysiology of aneuploidies were analyzed using MetaCore mapping tools.


RESULTS
Levels of apolipoprotein A1, AP-3mu, and antitrypsin were significantly decreased in trisomy-18 AFS, whereas placental protein-14 was increased. On the other hand, apolipoprotein A1 was decreased in trisomy-21 AFS, but antitrypsin, prealbumin, and transferrin were increased in trisomy 21. Biologic network analyses revealed that the proteins of the trisomy-18 AFS network were involved in immune processes, dysfunction of skin pigmentation, and platelet disorders, whereas those of trisomy 21 were associated with dysfunctional lipid and cholesterol metabolism, processes of metal ion transport, adenosine triphosphate metabolism, and energy-coupled protein transport.


CONCLUSIONS
The combined use of quantitative proteomics and functional network analyses may integrally analyze the pathophysiology of abnormal karyotypes.
Wang
Tzu-Hao
TH
Department of Obstetrics and Gynecology, Lin-Kou Medical Center, Chang Gung Memorial Hospital, Chang Gung University, 5 Fu-Hsing Street, Tao-Yuan, Taiwan.
Chao
An-Shine
AS
Chen
Jen-Kun
JK
Chao
Angel
A
Chang
Yao-Lung
YL
Cheng
Po-Jen
PJ
Chang
Shuenn-Dyh
SD
Wang
Hsin-Shih
HS
D000649:Amniocentesis / Q000379:methods; D000653:Amniotic Fluid / Q000166:cytology*; D000782:Aneuploidy; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007621:Karyotyping; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification; D012016:Reference Values; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014314:Trisomy / Q000235:genetics* / Q000473:pathology
D011506:Proteins