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Lysyl oxidase: A lung adenocarcinoma biomarker of invasion and survival
Author(s) -
Wilgus MayLin,
Borczuk Alain C.,
Stoopler Mark,
Ginsburg Mark,
Gorenstein Lyall,
Sonett Joshua R.,
Powell Charles A.
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.25768
Subject(s) - lysyl oxidase , medicine , adenocarcinoma , hazard ratio , autocrine signalling , paracrine signalling , immunohistochemistry , proportional hazards model , pathology , lung cancer , stromal cell , oncology , cancer , confidence interval , extracellular matrix , receptor , biology , microbiology and biotechnology
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.