Plasma levels of tissue inhibitor of matrix metalloproteinase-1correlate with diagnosis and prognosi

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Background There is no validated blood biomarker available for glioma management.Invasive growth is the key feature of glioma.We assessed the clinical usefulness of plasma tissue inhibitor of metalloproteinase 1 (TIMP-1),which has less molecular weight than metalloproteinases,as a potential blood biomarker for glioma.Methods A total of 285 patients and 59 normal subjects were studied.Plasma concentration of TIMP-1 was measured with enzyme-linked immunosorbent assay.Plasma TIMP-1 was compared between normal and glioma patients,between patients with different pathological grades,and between patients with different prognoses.Longitudinal changes in plasma TIMP-1 during treatment were also evaluated.Plasma matrix metalloproteinase (MMP)-9 level was also assayed and its clinical usefulness was compared with that of TIMP-1.Results Plasma TIMP-1 and MMP-9 were both increased in glioma patients compared with normal controls (TIMP-1:P <0.001; MMP-9:P=-0.007).Plasma TIMP-1 increases with increased tumor grade.In Grade Ⅳ gliomas,plasma TIMP-1 significantly increased after successful removal of the tumor (paired samples t-test,before operation vs.during chemotherapy without recurrence,t =-2.131,P=0.038),but did not change significantly at the time of tumor recurrence (during chemotherapy without recurrence vs.after tumor recurrence,t =-0.652,P=0.632).High plasma TIMP-1 level correlated with better survival in Grade Ⅳ glioma patients (hazard ratio:0.550,95% CI:0.101-1.000,P=0.036).In Grade Ⅳ gliomas,patients with higher plasma TIMP-1 had significantly longer survival time than those with lower plasma TIMP-1level (25.23 vs.18.95 months,log-rank P=0.045).Plasma MMP-9 did not show significant association with either the pathological grade or the prognosis of glioma patients.Conclusions Plasma TIMP-1 is associated with the diagnosis and prognosis of glioma patients.It appears to have better usefulness for guiding clinical decision making than plasma MMP-9.Further studies in an expanded patient population are needed to better define its clinical usefulness.
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