Ylisirniö S, Höyhtyä M, Turpeenniemi-Hujanen T
Department of Oncology, University of Oulu, Finland.
Anticancer Res. 2000 Mar-Apr;20(2B):1311-6.
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.
采用特异性单克隆抗体的酶联免疫吸附测定法（ELISA），对90例肺癌患者和20例对照者的血清/血浆中金属蛋白酶组织抑制剂（TIMP）-1和-2以及基质金属蛋白酶（MMP）-2和-9的免疫反应性蛋白进行定量分析。使用不同的ELISA分别检测游离MMP-2及其与抑制剂结合的形式，即MMP-2/TIMP-2复合物。对于MMP-9、TIMP-1和TIMP-2的检测，通过测量总蛋白来定量游离形式和复合物形式。与对照组相比，肺癌患者血清中TIMP-1、TIMP-2和MMP-2/TIMP-2复合物的蛋白水平存在显著差异。发现肺癌患者的TIMP-1水平高于对照组，而TIMP-2和MMP-2/TIMP-2复合物水平低于对照组血清。高TIMP-1（>300 ng/ml）或MMP-9（>30 ng/ml）与肺癌患者较差的累积生存率相关（对数秩检验P<0.05）。高TIMP-1提示预后不良，尤其是在鳞状细胞癌和III期非小细胞肺癌患者中：TIMP-1血清水平低的患者分别有66%和70%存活超过一年，而TIMP-1蛋白血清水平高的患者当时分别只有25%和20%存活。血浆MMP-9水平<30 ng/ml的肺癌患者中有56%存活12个月，而血浆MMP-9水平高的肺癌患者中只有31%存活超过一年。这种差异也具有显著性（对数秩分析，P<0.05）。我们的结果表明，金属蛋白酶系统的因素可能在肺癌进展中起重要作用。TIMP-1以及MMP-9可作为预后标志物，在为肺癌患者选择全身化疗或其他治疗方式时，其数值可在肺癌患者的随访中进行研究。
