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

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.

Figure 1

LOX and MMP2/MMP9 are positively expressed in resected NSCLC tumors. Total RNA extracted from 30 pairs of matched NSCLC samples was used for qRT-PCR analysis of mRNA expression. A. Upregulation of LOX mRNA expression in NSCLC tissues. The results were normalized to β-actin expression and expressed as fold change in tumor compared with matched N (P < 0.001). B. Positive correlation between LOX mRNA and MMP2 mRNA in NSCLC tissues (P = 0.002). C. Positive correlation between LOX mRNA and MMP9 mRNA in NSCLC tissues (P = 0.003). N: non-tumor tissue; T: tumor tissue.

Figure 2

Cytoplasm localization of LOX, MMP2 and MMP9 in NSCLC. Immunohistochemistry was performed to examine the expression of LOX, MMP2 and MMP9 protein in tumor tissues (×400). A. Positive expression of LOX protein in NSCLC. B. Positive expression of MMP2 in NSCLC. C. Positive expression of MMP9 in NSCLC. D. Negative expression of LOX protein in NSCLC. E. Negative expression of MMP2 protein in NSCLC. F. Negative expression of MMP9 protein in NSCLC.

Figure 3

Kaplan-Meier survival curves of overall survival in NSCLC patients based on LOX expression. Patients with high LOX expression had poorer overall survival rate as compared to those with low LOX expression.