ABSTRACT
There is evidence of the dysregulation of the balanced interaction between matrix metalloproteinases [MMPs] and their inhibitors, tissue inhibitors of metalloproteinases [TIMPs] in cancer which is thought to facilitate tumor cell invasion and metastasis. The role of MMP-9 and TIMP-1 was evaluated in different pathological types of lung cancer. Sera were collected from 52 lung cancer patients [10 had large cell carcinoma, 9 small cell carcinoma, 19 squamous cell carcinoma and 14 metastatic adenocarcinoma] as well as from 20 healthy control subjects. MMP-9 and TIMP-1 serum levels were measured using a sandwich enzyme immunoassay technique. Serum level of carcinoembryonic antigen [CEA] was also measured in the same subjects using a one step sandwich enzyme immunoassay technique. The study revealed a significant increase in the serum level of MMP9 in lung cancer patients as compared to controls [p < 0.001], with the highest value being found in patients with large cell carcinoma. A significant increase in TIMP-1 level was also found in lung cancer patients [p < 0.001], with no marked variation amongst different pathological types. A significant increase was also found in MMP9/T1MP1 ratio in patients versus controls [p < 0.001] with the highest value being measured in patients with large cell carcinoma. A significant positive correlation was found between the serum level of MMP-9 and TIMP-1 [r = 0.3, p < 0.05] and also with MMP-9/ TIMP-1 ratio [r - 0.99, p < 0.05] in lung cancer patients. Regarding CEA level, it showed a significant increase in lung cancer patients as compared to controls [p < 0.05], with the highest value being obtained from patients with squamous cell carcinoma. No significant correlation was found between CEA serum level and either MMP9 or TIMP1 [p > 0.05]. Analysis of the diagnostic value of CEA, MMP-9 and TIMP-1 in lung cancer patients revealed that CEA had 40.38% sensitivity, 100% specificity and positive predictive value [PPV], 39.2% negative predictive value [NPV] and 56.4% diagnostic efficiency [DE]. On the other hand, MMP-9 had 90.4% sensitivity, 95% specificity, 97.9% PPV, 82.6% NPV and 91.7% DE. The sensitivity, specificity, PPV, NPV and DE of TIMP-1 were 98.1%, 95%, 98.1%, 95% and 97.2% respectively. It can be concluded that increased serum levels of MMP-9, TIMP-1 and their ratio are found in lung cancer patients independently of CEA level. Both MMP-9 and TIMP-1 may serve as tumor markers, with TIMP-1 seems to be the most efficient with the highest diagnostic efficiency