Serum matrix metalloproteinases-2 and -9 and tissue inhibitor of matrix metalloproteinase-1 in non-small cell lung cancer patients: a potential role in tumour growth, invasion, and metastasis

ABSTRACT

The aim of this study was to measure senun levels of matrix metalloproteinases-2and -9 [MMP-2 and -9] and tissue inhibitor of matrix metalloproteinase-1 [TIMP-1] in non-small cell lung cancer [NSCLC] patients and to detect any potential role of these parameters in tumour growth, invasion and metastasis. The present study entailed 49 patients with primary NSCLC and 10 healthy non-smoker volunteers as a control group. All lung cancer patients were subjected to CT imaging and fiberoptic bronchoscopy with biopsy taking for histological diagnosis. Transthoracic fine needle aspiration lung biopsy or open lung biopsy was performed in patients with negative fiberoptic bronchoscopic results. Serum levels of MMP-2, MMP-9, and TIMP-1 were measured in both NSCLC patients and the controls by one-step sandwich enzyme immunoassay specific for each parameter. The current study revealed significant increase in the mean serum levels of MMP-2, MMP-9, and TIMP-1 in NSCLC patients than in the control group [P<0.0001]. It also revealed that 61.22%, 48.99%, and 53.06% of NSCLC patients had respectively serum MMP-2, MMP-9, and TIMP-1 levels higher than the corresponding cutoff values of the mean +2SD in the healthy controls. The study also showed significant positive association between the serum levels of these parameters and the TNM stage of the disease [P = 0.01, 0.03, and 0.01 for MMP-2, MMP-9, and TIMP-1 respectively]. The study also revealed significant differences in serum levels of such parameters in adenocarcinoma [AdC] versus squamous cell carcinoma [SqCC] [P = 0.03 for both MMP-2 and TIMP-1 and 0.02 for MMP-9]. Serum levels of MMP-2, MMP-9, and TIMP-1 are elevated in NSCLC patients and are associated with the TNM stage of the disease suggesting important roles of such parameters in growth, invasion, and metastasis of NSCLC. The elevated levels of such parameters in AdC than in SqCC may relate to the greater tendency of the former for systemic metastasis. This study suggests that serum MMP-2, MMP-9, and TIMP-1 may be used as useful markers of NSCLC invasion and metastasis