Whole blood gene expression profile associated with spontaneous preterm birth in women with threatened preterm labor.
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.
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Yujing Jan
YJ
Heng
School of Women's and Infants' Health, University of Western Australia, Crawley, WA, Australia.
Craig Edward
CE
Pennell
Institute for Infocomm Research, Agency for Science, Technology and Research, Singapore, Singapore.
Hon Nian
HN
Chua
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Jonathan Edward
JE
Perkins
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Stephen James
SJ
Lye
D000033:Abortion, Threatened / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D000328:Adult; D001773:Blood Cells / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000097:blood / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007752:Obstetric Labor, Premature / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood / Q000235:genetics*; D047929:Term Birth / Q000097:blood / Q000235:genetics
C403421:FFN protein, human; D005353:Fibronectins