title: Genome-wide expression profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in human intestinal tissues: dysregulation of functional pathways.
abstract: OBJECTIVE
  To provide a comprehensive database of gene regulation and compare differentially regulated molecular networks in human tissues of necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP).
  
  
  BACKGROUND
  Both NEC and SIP are devastating surgical emergencies associated with high morbidity and mortality in preterm infants. Their pathophysiology and molecular mechanisms remain unclear.
  
  
  METHODS
  Differential whole genome microarray analysis was performed on intestinal tissues collected from NEC (n = 15) and SIP (n = 12) infants and compared with tissues collected from surgical-control patients with noninflammatory intestinal conditions (n = 14). Validation of 52 target gene expressions was performed by quantitative polymerase chain reaction. Regulatory networks of significantly affected genes were constructed according to functional pathways.
  
  
  RESULTS
  Extensive and significant changes of gene expression were observed in NEC tissues, which comprised multiple pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia and oxidative stress, inflammation, and muscle contraction. These dysregulated genes could be networked downstream of key receptors, TLR2, TLR4, and TREM1, and mediated via NF-κB, AP-1, and HIF1A transcription factor pathways, indicating predominant microbial and inflammatory involvement. In contrast, SIP tissues exhibited much milder and less diversified expressional changes, with target genes significantly associated with G-protein-mediated muscle contraction and extracellular matrix remodeling.
  
  
  CONCLUSIONS
  The molecular evidence suggests that NEC and SIP are likely 2 different diseases caused by distinct etiology and pathophysiology. This first comprehensive database on differential gene expression profiles of human NEC and SIP tissues could lead to development of disease-specific diagnostic and prognostic biomarkers and new therapeutic strategies for improving outcomes.
authors.affiliation: Departments of *Paediatrics †Surgery ‡Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors.forename: Kathy Yuen Yee
authors.initials: KY
authors.lastname: Chan
authors.forename: Kam Tong
authors.initials: KT
authors.lastname: Leung
authors.forename: Yuk Him
authors.initials: YH
authors.lastname: Tam
authors.forename: Hugh Simon
authors.initials: HS
authors.lastname: Lam
authors.forename: Hon Ming
authors.initials: HM
authors.lastname: Cheung
authors.forename: Terence Ping Yuen
authors.initials: TP
authors.lastname: Ma
authors.forename: Kim Hung
authors.initials: KH
authors.lastname: Lee
authors.forename: Ka Fai
authors.initials: KF
authors.lastname: To
authors.forename: Karen
authors.initials: K
authors.lastname: Li
authors.forename: Pak Cheung
authors.initials: PC
authors.lastname: Ng
mesh_terms: D020345:Enterocolitis, Necrotizing / Q000235:genetics* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D018507:Gene Expression Regulation, Developmental; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007416:Intestinal Perforation / Q000235:genetics* / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger