Serum tissue inhibitors of metalloproteinase-1 and -2 in patients with non-small cell lung cancer

Purpose. In view of the increasing number of patients diagnosed with lung cancer every year worldwide, there is an urgent need for an effective screening marker to improve its early detection. Methods. We quantified the level of immunoreactive proteins for the tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in the sera of 54 patients with non-small cell lung cancer (NSCLC) and 25 healthy control subjects, by using enzyme-linked immunosorbent assays with specific monoclonal antibodies. Results. The TIMP-1 level was significantly higher, and the TIMP-2 level was significantly lower in the patients with NSCLC than in the controls. Furthermore, both TIMP-1 and TIMP-2 were significantly higher in patients with squamous cell carcinoma than in those with adenocarcinoma. The TIMP-1 level in patients with stage III/IV disease was significantly higher than that in those with stage I/II disease. The TIMP-1/TIMP-2 ratio was significantly higher in the patients with NSCLC, and the receiver-operating characteristic curves analysis revealed that the TIMP-1/2 ratio, but not TIMP-1 or -2 alone, was a better screening marker for NSCLC than carcinoembryonic antigen (P < 0.0001). Patients with a high TIMP-1 value had significantly shorter disease-free survival (P = 0.0479), but those with a high TIMP-1/2 ratio did not. Conclusion. The TIMP-1/2 ratio may be a good screening marker of NSCLC; however, it was less effective than TIMP-1 as a prognostic factor.