Te-Yao Hsu1, Kuo-Wang Tsai2, Kuo-Chung Lan3, Hsuan-Ning Hung4, Yun-Ju Lai5, Hsin-Hsin Cheng6, Chih-Chang Tsai7, Sung-Chou Li8. 1. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: tyhsu@cgmh.org.tw. 2. Department of Research, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan. Electronic address: kwtsai6733@gmail.com. 3. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: ankuochung@gmail.com. 4. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: agneshenrysean@gmail.com. 5. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: lusionbear@cgmh.org.tw. 6. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: chokovarous@cgmh.org.tw. 7. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: aniki@cgmh.org.tw. 8. Genomics and Proteomics Core Laboratory, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: raymond.pinus@gmail.com.
Abstract
OBJECTIVE: Preterm birth severely threatens neonatal health and life. Although the detailed mechanism of preterm birth is not well understood, accurately predicting preterm birth can help people make preparations in advance, greatly reducing the subsequent health risk of neonates. Therefore, in this study, we aimed to identify potential protein biomarkers of preterm birth in amniotic fluid (AF). MATERIALS AND METHODS: We first enrolled pregnant subjects and collected their AF samples when they underwent amniocentesis at the second trimester of gestation. After delivery, the collected AF samples were classified into a full-term birth (sample size n = 21) set or preterm birth (n = 36) set, followed by 2-D DIGE and MS/MS assays. RESULTS: By doing so, we identified seven potential protein biomarkers of preterm birth, three of which were further validated in all samples with ELISA, including Apolipoprotein A-IV (Apoa4), Lumican (Lum) and Kininogen-1 (Kng1). As a result, all three potential biomarkers were significantly differently expressed between preterm and full-term birth AF samples. Furthermore, without prior classification, we found that these three biomarkers were positively correlated with gestation age (correlation coefficient ranging from 0.25 to 0.38) and were able to predict the occurrence of preterm birth. CONCLUSION: In this study, by examining amniotic fluid, we identified three biomarker proteins that may facilitate the identification of preterm birth. There three proteins were never reported to be related to preterm birth. Their pathogenesis roles in preterm birth deserve further investigations by using in vitro cell model or in vivo animal model assays.
OBJECTIVE: Preterm birth severely threatens neonatal health and life. Although the detailed mechanism of preterm birth is not well understood, accurately predicting preterm birth can help people make preparations in advance, greatly reducing the subsequent health risk of neonates. Therefore, in this study, we aimed to identify potential protein biomarkers of preterm birth in amniotic fluid (AF). MATERIALS AND METHODS: We first enrolled pregnant subjects and collected their AF samples when they underwent amniocentesis at the second trimester of gestation. After delivery, the collected AF samples were classified into a full-term birth (sample size n = 21) set or preterm birth (n = 36) set, followed by 2-D DIGE and MS/MS assays. RESULTS: By doing so, we identified seven potential protein biomarkers of preterm birth, three of which were further validated in all samples with ELISA, including Apolipoprotein A-IV (Apoa4), Lumican (Lum) and Kininogen-1 (Kng1). As a result, all three potential biomarkers were significantly differently expressed between preterm and full-term birth AF samples. Furthermore, without prior classification, we found that these three biomarkers were positively correlated with gestation age (correlation coefficient ranging from 0.25 to 0.38) and were able to predict the occurrence of preterm birth. CONCLUSION: In this study, by examining amniotic fluid, we identified three biomarker proteins that may facilitate the identification of preterm birth. There three proteins were never reported to be related to preterm birth. Their pathogenesis roles in preterm birth deserve further investigations by using in vitro cell model or in vivo animal model assays.