Lysyl oxidase: A lung adenocarcinoma biomarker of invasion and survival

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. Cancer 2011. © 2010 American Cancer Society.