Serum TIMP-1 in gastric cancer patients: a potential prognostic biomarker

Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is over-expressed in many human malignancies, including gastric cancer, and is associated with poor outcome. The purpose of this study was to evaluate the clinical and prognostic significance of preoperative serum TIMP-1 levels in gastric cancer patients. One hundred and seventy gastric cancer patients who underwent gastrectomy between 1996 and 2001 were enrolled in this study. The serum concentration of TIMP-1 protein in these patients and in 116 healthy controls was determined using an enzyme-linked immunoassay (ELISA). When a serum TIMP-1 level >95 percentile of healthy controls was set as the upper cut-off value (348.8 ng/ml), abnormally high serum TIMP-1 were observed in 29 (17.1%) of the gastric cancer patients vs 4.3% of healthy controls (p<0.001). The sensitivity and specificity of serum TIMP-1 as a diagnostic tumor marker were 17.1% and 97.7%, respectively. Serum TIMP-1 was positively associated with morphologic appearance (Borrmann type), tumor size, depth of wall invasion, lymph node metastasis, liver metastasis, and peritoneal seeding. It was also positively associated with lymphatic invasion, perineural invasion, and pathological stage. It was not significantly associated with age, gender, tumor location, or histological type. A higher serum TIMP-1 group was significantly associated with lower survival rates than the lower serum TIMP-1 group (cut-off value at the median; 5-yr survival rate: 32.3% vs 55.6%, log-rank p = 0.0011). When the patients were divided into 2 groups using the 95 percentile TIMP-1 level of controls as the cut-off value, 5-yr survival rates were 24.6% and 47.5% respectively for the higher and lower TIMP-1 groups (log rank p = 0.0147). An elevated preoperative level of serum TIMP-1 was significantly associated with progressive disease, advanced stage, and worse survival in gastric cancer patients. Although it is not a good marker for diagnosis, elevated serum TIMP-1 level shows promise as a marker for prognosis in patients with gastric cancer.