Correlations of lysyl oxidase with MMP2/MMP9 expression and its prognostic value in non-small cell lung cancer

Int J Clin Exp Pathol. 2014 Aug 15;7(9):6040-7. eCollection 2014.

Abstract

Lysyl oxidase (LOX) has been reported to regulate tumor metastasis and has been found to involve in modification of extracellular matrix (ECM) in the context of tumorigenesis. The aim of this study is to determine the prognostic significance of LOX in non-small cell lung cancer (NSCLC) patients and to examine the correlation between LOX expression and ECM remodeling-associated MMP2/MMP9 in NSCLC tissues. The mRNA expression of LOX, MMP2 and MMP9 was investigated by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) in 30 NSCLC patients. The protein expression of LOX was measured by immunohistochemistry (IHC) in 110 paraffin-embedded tissues with NSCLC and the protein expression of MMP2/MMP9 was measured by in 30 NSCLC patients. The correlation between LOX expression and clinical parameters and MMP2/MMP9 was analyzed by appropriate statistics. The Kaplan-Meier method, univariate and multivariate regression analysis was used to analyze the correlation between LOX expression and overall survival (OS). The relative mRNA expression or protein expression of LOX were significantly higher in NSCLC tumor tissues than in the corresponding noncancerous tissues (P < 0.05). High LOX expression was significantly associated with MMP2, MMP9, tumor size, lymph node metastasis, pathological stage and OS (P < 0.05). Univariate and multivariate analysis showed that LOX was an independent prognostic factor for OS. Our results indicate that LOX may play a role in the metastasis of NSCLC by promoting MMP2/MMP9 expression. LOX expression is an independent prognostic factor in OS in NSCLC.

Keywords: ECM; LOX; NSCLC; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Chi-Square Distribution
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 2 / analysis*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / analysis*
  • Matrix Metalloproteinase 9 / genetics
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Protein-Lysine 6-Oxidase / analysis*
  • Protein-Lysine 6-Oxidase / genetics
  • RNA, Messenger / analysis
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Time Factors
  • Tumor Burden
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • Protein-Lysine 6-Oxidase
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9