title: Lysyl oxidase: a lung adenocarcinoma biomarker of invasion and survival.
abstract: BACKGROUND
  Lung adenocarcinoma invasion and metastasis arises from autocrine and paracrine signaling events between tumor epithelial cells and the stromal microenvironment that is mediated in part by transforming growth factor-β (TGF-β) signaling. The copper-dependent amine oxidase lysyl oxidase (LOX) plays a role in extracellular matrix structure and is up-regulated in invasive type II TGF-β receptor-deficient cells. The authors hypothesized that LOX expression is associated with extent of invasion and survival in patients with lung adenocarcinoma.
  
  
  METHODS
  LOX immunohistochemical staining was examined in 166 surgically resected lung adenocarcinomas and results were correlated with clinicopathological features and survival.
  
  
  RESULTS
  High-intensity LOX staining was found to be associated with the linear extent of invasion (Spearman correlation coefficient = 0.2; P = .01). There was an association between high LOX staining and decreased 5-year survival observed within the entire cohort (log-rank P < .001) and among the patients with stage I disease (n = 119; P < .001). Cox proportional hazards regression analysis confirmed that LOX was a significant prognostic indicator of increased risk of 5-year mortality for all patients (hazard ratio [HR], 2.55; 95% confidence interval [95% CI], 1.51-4.30 [P < .001]) and for patients with Stage I disease (HR, 3.51; 95% CI, 1.77-6.99 [P < .001]). LOX expression was found to be independently associated with risk of death after adjustment for relevant covariates (HR, 2.29; 95% CI, 1.33-3.94 [P = .003]).
  
  
  CONCLUSIONS
  Higher expression of LOX is associated with invasion and is an independent predictor of poor prognosis in patients with early stage lung adenocarcinoma.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care, Columbia University Medical Center, New York, New York, USA.
authors.forename: May-Lin
authors.initials: ML
authors.lastname: Wilgus
authors.forename: Alain C
authors.initials: AC
authors.lastname: Borczuk
authors.forename: Mark
authors.initials: M
authors.lastname: Stoopler
authors.forename: Mark
authors.initials: M
authors.lastname: Ginsburg
authors.forename: Lyall
authors.initials: L
authors.lastname: Gorenstein
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sonett
authors.forename: Charles A
authors.initials: CA
authors.lastname: Powell
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D008249:Protein-Lysine 6-Oxidase