Signature pathways identified from gene expression profiles in the human uterine cervix before and after spontaneous term parturition.
OBJECTIVE
This study aimed to discover "signature pathways" that characterize biologic processes, based on genes differentially expressed in the uterine cervix before and after spontaneous labor.


METHODS
The cervical transcriptome was characterized previously from biopsy specimens taken before and after term labor. Pathway analysis was used to study the differentially expressed genes, based on 2 gene-to-pathway annotation databases (Kyoto Encyclopedia of Genes and Genomes [Kanehisa Laboratories, Kyoto University, Kyoto, Japan] and Metacore software [GeneGo, Inc, St. Joseph, MI]). Overrepresented and highly impacted pathways and connectivity nodes were identified.


RESULTS
Fifty-two pathways in the Metacore database were enriched significantly in differentially expressed genes. Three of the top 5 pathways were known to be involved in cervical remodeling. Two novel pathways were plasmin signaling and plasminogen activator urokinase signaling. The same analysis with the Kyoto Encyclopedia of Genes and Genomes database identified 4 significant pathways that the impact analysis confirmed. Multiple nodes that provide connectivity within the plasmin and plasminogen activator urokinase signaling pathways were identified.


CONCLUSIONS
Three strategies for pathway analysis were consistent in their identification of novel, unexpected, and expected pathways, which suggests that this approach is both valid and effective for the elucidation of biologic mechanisms that are involved in cervical dilation and remodeling.
Hassan
Sonia S
SS
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA. shassan@med.wayne.edu
Romero
Roberto
R
Tarca
Adi L
AL
Draghici
Sorin
S
Pineles
Beth
B
Bugrim
Andrej
A
Khalek
Nahla
N
Camacho
Natalia
N
Mittal
Pooja
P
Yoon
Bo Hyun
BH
Espinoza
Jimmy
J
Kim
Chong Jai
CJ
Sorokin
Yoram
Y
Malone
John
J
D002584:Cervix Uteri / Q000502:physiology*; D002585:Cesarean Section; D003430:Cross-Sectional Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007743:Labor, Obstetric / Q000235:genetics*; D011247:Pregnancy; D015398:Signal Transduction / Q000235:genetics*; D047929:Term Birth / Q000235:genetics*