Serum matrix metalloproteinases -2, -9 and tissue inhibitor of metalloproteinases -1, -2 in lung cancer

TIMP-1 as a prognoctic marker

S. Ylisirniö, Matti Höyhtyä, T. Turpeenniemi-Hujanen

Research output: Contribution to journalArticleScientificpeer-review

156 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1311 - 1316
Number of pages6
JournalAnticancer Research
Volume20
Publication statusPublished - 2000
MoE publication typeA1 Journal article-refereed

Fingerprint

Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Lung Neoplasms
Serum
Tissue Inhibitor of Metalloproteinases
Squamous Cell Neoplasms
Proteins
Metalloproteases
Immunoenzyme Techniques
Blood Proteins
Enzyme-Linked Immunosorbent Assay
Monoclonal Antibodies
Drug Therapy

Cite this

Ylisirniö, S. ; Höyhtyä, Matti ; Turpeenniemi-Hujanen, T. / Serum matrix metalloproteinases -2, -9 and tissue inhibitor of metalloproteinases -1, -2 in lung cancer : TIMP-1 as a prognoctic marker. In: Anticancer Research. 2000 ; Vol. 20. pp. 1311 - 1316.
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title = "Serum matrix metalloproteinases -2, -9 and tissue inhibitor of metalloproteinases -1, -2 in lung cancer: TIMP-1 as a prognoctic marker",
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.",
author = "S. Ylisirni{\"o} and Matti H{\"o}yhty{\"a} and T. Turpeenniemi-Hujanen",
year = "2000",
language = "English",
volume = "20",
pages = "1311 -- 1316",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",

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Serum matrix metalloproteinases -2, -9 and tissue inhibitor of metalloproteinases -1, -2 in lung cancer : TIMP-1 as a prognoctic marker. / Ylisirniö, S.; Höyhtyä, Matti; Turpeenniemi-Hujanen, T.

In: Anticancer Research, Vol. 20, 2000, p. 1311 - 1316.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Serum matrix metalloproteinases -2, -9 and tissue inhibitor of metalloproteinases -1, -2 in lung cancer

T2 - TIMP-1 as a prognoctic marker

AU - Ylisirniö, S.

AU - Höyhtyä, Matti

AU - Turpeenniemi-Hujanen, T.

PY - 2000

Y1 - 2000

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.

AB - 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.

UR - https://www.ncbi.nlm.nih.gov/pubmed/10810441

M3 - Article

VL - 20

SP - 1311

EP - 1316

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

ER -