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Serum matrix metalloproteinases -2, -9 and tissue inhibitors of metalloproteinases -1, -2 in lung cancer--TIMP-1 as a prognostic marker.
Anticancer Res. 2000 Mar-Apr; 20(2B):1311-6.AR

Abstract

The immunoreactive protein for the tissue inhibitor of the metalloproteinase (TIMP)-1 and -2 as well as for the matrix metalloproteinase (MMP)-2 and -9 was quantified from the sera/plasma of 90 lung cancer patients and 20 control subjects with enzyme linked immunoassays (ELISA) using specific monoclonal antibodies. Free MMP-2 and that bound to the inhibitor, the MMP-2/TIMP-2 complex were measured separately using different ELISAs. For the detection of MMP-9, TIMP-1 and TIMP-2, the total protein was measured to quantify both free and complex forms. Serum protein levels for TIMP-1, TIMP-2 and the MMP-2/TIMP-2 complex differed significantly in patients with lung cancer when compared to controls. TIMP-1 levels were found to be higher in lung cancer than in controls, whereas TIMP-2 and MMP-2/TIMP-2 complex levels were lower in lung cancer than in the sera of the control subjects. High TIMP-1 (> 300 ng/ml) or MMP-9 (> 30 ng/ml) correlated to poor cumulative survival in lung cancer patients (log rank P < 0.05). High TIMP-1 indicated a poor prognosis, especially in squamous cell cancer and in NSCLC patients with stage III: 66% and 70%, respectively, of the patients with low TIMP-l serum levels survived for more than one year, when only 25% and 20%, respectively, of the patients with high serum levels for TIMP-1 protein survived at that time. 56% of lung cancer patients with a plasma MMP-9 level < 30 ng/ml survived for 12 months when only 31% of the lung cancer patients with high MMP-9 plasma levels survived for more than one year. Also this difference was significant (log rank analysis, P < 0.05). Our results suggest that the factors of the metalloproteinase system might be important in lung cancer progression. TIMP-1 as well as MMP-9 could serve as prognostic markers, and their values could be investigated in the follow-up of lung cancer patients when selecting patients for systemic chemotherapy or other treatment modalities.

Authors+Show Affiliations

Department of Oncology, University of Oulu, Finland.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10810441

Citation

Ylisirniö, S, et al. "Serum Matrix Metalloproteinases -2, -9 and Tissue Inhibitors of Metalloproteinases -1, -2 in Lung cancer--TIMP-1 as a Prognostic Marker." Anticancer Research, vol. 20, no. 2B, 2000, pp. 1311-6.
Ylisirniö S, Höyhtyä M, Turpeenniemi-Hujanen T. Serum matrix metalloproteinases -2, -9 and tissue inhibitors of metalloproteinases -1, -2 in lung cancer--TIMP-1 as a prognostic marker. Anticancer Res. 2000;20(2B):1311-6.
Ylisirniö, S., Höyhtyä, M., & Turpeenniemi-Hujanen, T. (2000). Serum matrix metalloproteinases -2, -9 and tissue inhibitors of metalloproteinases -1, -2 in lung cancer--TIMP-1 as a prognostic marker. Anticancer Research, 20(2B), 1311-6.
Ylisirniö S, Höyhtyä M, Turpeenniemi-Hujanen T. Serum Matrix Metalloproteinases -2, -9 and Tissue Inhibitors of Metalloproteinases -1, -2 in Lung cancer--TIMP-1 as a Prognostic Marker. Anticancer Res. 2000 Mar-Apr;20(2B):1311-6. PubMed PMID: 10810441.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum matrix metalloproteinases -2, -9 and tissue inhibitors of metalloproteinases -1, -2 in lung cancer--TIMP-1 as a prognostic marker. AU - Ylisirniö,S, AU - Höyhtyä,M, AU - Turpeenniemi-Hujanen,T, PY - 2000/5/16/pubmed PY - 2000/6/3/medline PY - 2000/5/16/entrez SP - 1311 EP - 6 JF - Anticancer research JO - Anticancer Res VL - 20 IS - 2B N2 - The immunoreactive protein for the tissue inhibitor of the metalloproteinase (TIMP)-1 and -2 as well as for the matrix metalloproteinase (MMP)-2 and -9 was quantified from the sera/plasma of 90 lung cancer patients and 20 control subjects with enzyme linked immunoassays (ELISA) using specific monoclonal antibodies. Free MMP-2 and that bound to the inhibitor, the MMP-2/TIMP-2 complex were measured separately using different ELISAs. For the detection of MMP-9, TIMP-1 and TIMP-2, the total protein was measured to quantify both free and complex forms. Serum protein levels for TIMP-1, TIMP-2 and the MMP-2/TIMP-2 complex differed significantly in patients with lung cancer when compared to controls. TIMP-1 levels were found to be higher in lung cancer than in controls, whereas TIMP-2 and MMP-2/TIMP-2 complex levels were lower in lung cancer than in the sera of the control subjects. High TIMP-1 (> 300 ng/ml) or MMP-9 (> 30 ng/ml) correlated to poor cumulative survival in lung cancer patients (log rank P < 0.05). High TIMP-1 indicated a poor prognosis, especially in squamous cell cancer and in NSCLC patients with stage III: 66% and 70%, respectively, of the patients with low TIMP-l serum levels survived for more than one year, when only 25% and 20%, respectively, of the patients with high serum levels for TIMP-1 protein survived at that time. 56% of lung cancer patients with a plasma MMP-9 level < 30 ng/ml survived for 12 months when only 31% of the lung cancer patients with high MMP-9 plasma levels survived for more than one year. Also this difference was significant (log rank analysis, P < 0.05). Our results suggest that the factors of the metalloproteinase system might be important in lung cancer progression. TIMP-1 as well as MMP-9 could serve as prognostic markers, and their values could be investigated in the follow-up of lung cancer patients when selecting patients for systemic chemotherapy or other treatment modalities. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/10810441/Serum_matrix_metalloproteinases__2__9_and_tissue_inhibitors_of_metalloproteinases__1__2_in_lung_cancer__TIMP_1_as_a_prognostic_marker_ L2 - http://www.diseaseinfosearch.org/result/4334 DB - PRIME DP - Unbound Medicine ER -