BACKGROUNDThere 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.

METHODSA 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.

RESULTSPlasma 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-1 level (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.

CONCLUSIONSPlasma 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.