Elevated expression of MMP-2 and TIMP-2 cooperatively correlates with risk of lung cancer.

Chao Cao,Ning Xu,Xiaoping Huang,Wenxue Zhang,Tianwen Lai,Zaichun Deng,Xiaoxia Zheng

doi:10.18632/oncotarget.20156

Abstract

Lung cancer is one of the most common form of malignant diseases and the leading cause of cancer-related mortality worldwide. It is reported that approximately two-thirds of lung cancer patients is the presence of advance disease at the time of diagnosis. Hence novel lung cancer diagnostic tests, which can be used to screen individuals at high risk, are required. In the derivation cohort, a total of 88 patients admitted into hospital with suspected lung cancer were included. Bronchial alveolar lavage fluid (BALF) and lung tissue samples were collected from included patients, and were analyzed for MMP-2 and TIMP-2 expression. The results showed a higher level of MMP-2 and TIMP-2 expression and secretion in airways of lung cancer patients than that of benign diseases. A statistically significant correlation was observed between MMP-2 and TIMP-2. In addition, a validation cohort involving 107 patients was conducted to confirm these results. Interesting, BALF MMP-2 and TIMP-2 showed a high sensitivity and specificity in predicting the malignant nature of pulmonary disease in both derivation cohort and validation cohort. The findings in this study suggested that elevated expression of MMP-2 and TIMP-2 cooperatively correlates with risk of lung cancer. Measurement of MMP-2 and TIMP-2 in BALF might be helpful for differential diagnosis of primary lung cancer.

Highlights

Lung cancer accounts for nearly one fifth of the cancer related deaths worldwide [1]
The results showed a higher level of Matrix metalloproteinases (MMPs)-2 and TIMP-2 expression and secretion in airways of lung cancer patients than that of benign diseases
We performed the present study to evaluate the expression of MMP-2 and TIMP-2 in airways of lung cancer patients by comparing levels of them in benign diseases

Summary

Introduction

Lung cancer accounts for nearly one fifth of the cancer related deaths worldwide [1]. It is reported that 5-year survival rate is only 15% for patients diagnosed with lung cancer in the advanced stage [3]. There is a great need to identify lung cancer at an early stage, ideally before cancer cells invasion and metastasis. This has led to significant interest in high sensitivity and specificity screening methods to detect early-stage cancers, for individuals with high risk. More than 20 members of the MMP family were identified, among which MMP-2 has been extensively studied in human cancers and has been shown to be closely related to the invasive potential and metastasis of different types of tumor cells including lung cancer [5,6,7]. The expression of MMP-2 and its inhibitor the tissue inhibitors of matrix metalloproteinase www.impactjournals.com/oncotarget

Methods

Results

Conclusion