Elevated serum levels of type I collagen degradation marker ICTP and tissue inhibitor of metalloproteinase (TIMP) 1 are associated with poor prognosis in lung cancer

Purpose: The aim of this study was to evaluate the correlation between type I collagen degradation marker ICTP, MMP (matrix metalloproteinase)-9, and tissue inhibitor of metalloproteinase (TIMP)-1 and to compare their value a s prognostic factors in lung cancer. Experimental Design: From the sera of 141 lung cancer patients, we assessed markers of type I collagen synthesis (PINP and PICP) and degradation (ICTP ) by radioimmunoassays, and we assessed MMP-9 and its tissue inhibitor TIMP -1 by ELISA, There were 62 squamous cell carcinomas, 42 adenocarcinomas, 14 small cell carcinomas, and 23 cases with other histology, Seventeen of the se patients had advanced disease. Sixty-seven patients had been operated on , 33 had received radiation therapy, 7 had received chemotherapy, and the r est had received other treatment combinations, Results: We examined the relationship between these markers and found a cor relation between ICTP and MMP-9 (r = 0.201; P = 0.01) or TIMP-1 (r = 0.415; P = 0.00), Elevated serum concentrations of ICTP (>5 mug/liter) and/or TIM P-1 (> 300 ng/ml) correlated with poor prognosis, In univariate regression analysis, ICTP had prognostic value (odds ratio, 1.6362; P < 0.03): the pat ients with elevated serum concentrations of ICTP (>5 mug/liter) had a 64% h igher risk of dying from lung cancer than did patients with opposite values . Conclusions: Our results indicated that ICTP and TIMP-1 are good prognostic markers in lung cancer. The association between serum MMP-9 and ICTP sugge sts that MMP-9 could play a role in the degradation of the extracellular ma trix producing ICTP in this pathological situation.