Heng Yujing Jan, Pennell Craig Edward, Chua Hon Nian, Perkins Jonathan Edward, Lye Stephen James
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
School of Women's and Infants' Health, University of Western Australia, Crawley, WA, Australia.
PLoS One. 2014 May 14;9(5):e96901. doi: 10.1371/journal.pone.0096901. eCollection 2014.
Threatened preterm labor (TPTL) is defined as persistent premature uterine contractions between 20 and 37 weeks of gestation and is the most common condition that requires hospitalization during pregnancy. Most of these TPTL women continue their pregnancies to term while only an estimated 5% will deliver a premature baby within ten days. The aim of this work was to study differential whole blood gene expression associated with spontaneous preterm birth (sPTB) within 48 hours of hospital admission. Peripheral blood was collected at point of hospital admission from 154 women with TPTL before any medical treatment. Microarrays were utilized to investigate differential whole blood gene expression between TPTL women who did (n = 48) or did not have a sPTB (n = 106) within 48 hours of admission. Total leukocyte and neutrophil counts were significantly higher (35% and 41% respectively) in women who had sPTB than women who did not deliver within 48 hours (p<0.001). Fetal fibronectin (fFN) test was performed on 62 women. There was no difference in the urine, vaginal and placental microbiology and histopathology reports between the two groups of women. There were 469 significant differentially expressed genes (FDR<0.05); 28 differentially expressed genes were chosen for microarray validation using qRT-PCR and 20 out of 28 genes were successfully validated (p<0.05). An optimal random forest classifier model to predict sPTB was achieved using the top nine differentially expressed genes coupled with peripheral clinical blood data (sensitivity 70.8%, specificity 75.5%). These differentially expressed genes may further elucidate the underlying mechanisms of sPTB and pave the way for future systems biology studies to predict sPTB.
先兆早产（TPTL）的定义为妊娠20至37周期间持续出现的子宫过早收缩，是孕期最常见的需要住院治疗的情况。这些TPTL女性中的大多数会继续妊娠至足月，而估计只有5%的人会在十天内早产。这项研究的目的是研究与入院48小时内自发早产（sPTB）相关的全血基因差异表达。在154名未经任何药物治疗的TPTL女性入院时采集外周血。利用微阵列研究入院48小时内发生（n = 48）或未发生（n = 106）sPTB的TPTL女性之间的全血基因差异表达。发生sPTB的女性的总白细胞和中性粒细胞计数显著更高（分别为35%和41%），高于48小时内未分娩的女性（p<0.001）。对62名女性进行了胎儿纤连蛋白（fFN）检测。两组女性的尿液、阴道和胎盘微生物学及组织病理学报告没有差异。有469个显著差异表达基因（FDR<0.05）；选择了28个差异表达基因进行qRT-PCR微阵列验证，28个基因中有20个成功验证（p<0.05）。使用前九个差异表达基因结合外周临床血液数据建立了一个预测sPTB的最佳随机森林分类器模型（敏感性70.8%，特异性75.5%）。这些差异表达基因可能进一步阐明sPTB的潜在机制，并为未来预测sPTB的系统生物学研究铺平道路。
