title: Clinical significance of mTOR, ZEB1, ROCK1 expression in lung tissues of pulmonary fibrosis patients.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown causes. Three proteins (mammalian target of rapamycin, mTOR; zinc finger E-box-binding homeobox 1, ZEB1; Rho-associated, coiled-coil containing protein kinase 1, ROCK1) may be related to pulmonary fibrosis. However, they have not been assessed in human pulmonary fibrosis. We assessed the clinical significance of mTOR, ZEB1, and ROCK1 expression in human pulmonary fibrosis of usual interstitial pneumonia (UIP) pattern.
  
  
  METHODS
  The mTOR, ZEB1, and ROCK1 expression was evaluated by immunohistochemical staining of 30 surgical lung biopsy tissues from 26 IPF and 4 UIP pattern connective tissue disease related interstitial lung disease (CTD-ILD) patients. The expression scores correlated with the clinical features.
  
  
  RESULTS
  The mTOR, ZEB1 and ROCK1 mainly expressed in alveolar epithelial cells of UIP lungs. The histological fibrosis scores and lung function decline in the strong mTOR expression group were higher than those in the weak and intermediate expression group. Patients with positive ZEB1 expression had higher fibrosis scores and greater decline in carbon monoxide diffusion capacity (DLCO) than patients with negative ZEB1 expression. Patients with positive mTOR or ZEB1 expression had poorer prognosis than that of patients with negative mTOR or ZEB1 expression, although it was not statistically significant. ROCK1 was not associated with the studied clinicopathological features.
  
  
  CONCLUSIONS
  The mTOR and ZEB1 expression in pulmonary fibrosis patients significantly correlated with the fibrosis score and lung function decline, indicating that it may be related to the prognosis of pulmonary fibrosis. Further studies involving large numbers of homogeneous IPF patients are warranted.
authors.forename: Jong Sun
authors.initials: JS
authors.lastname: Park
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Young Sik
authors.initials: YS
authors.lastname: Park
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Jae-Joon
authors.initials: JJ
authors.lastname: Yim
authors.forename: Chul-Gyu
authors.initials: CG
authors.lastname: Yoo
authors.forename: Sung Koo
authors.initials: SK
authors.lastname: Han
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea. ywkim@snu.ac.kr.
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D002248:Carbon Monoxide; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011650:Pulmonary Alveoli / Q000737:chemistry; D011653:Pulmonary Diffusing Capacity; D020545:Respiratory Mucosa / Q000737:chemistry; D058570:TOR Serine-Threonine Kinases / Q000032:analysis*; D014157:Transcription Factors / Q000032:analysis*; D000071799:Zinc Finger E-box-Binding Homeobox 1; D054460:rho-Associated Kinases / Q000032:analysis*
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D002248:Carbon Monoxide; C546842:MTOR protein, human; C515851:ROCK1 protein, human; D058570:TOR Serine-Threonine Kinases; D054460:rho-Associated Kinases