血浆金属蛋白酶组织抑制剂1水平与胶质瘤患者诊断及预后相关

背景：目前在胶质瘤的治疗中没有可用的血液标志物。侵袭性生长是胶质瘤的重要特征。我们评估了具有小分子量的血浆蛋白酶组织抑制剂1的临床意义及其作为血液生物标志物的前景。方法：共研究了285例患者和59例正常人。采用酶联免疫吸附法检测了血浆TIMP-1浓度。比较了正常人和胶质瘤、胶质瘤不同级别之间、不同预后的患者血浆TIMP-1的差异,并评估了血浆TIIMP-1在治疗过程中的变化。我们还检测了血浆MMP-9的浓度,评估了其临床意义并与TIMP-1做了比较。结果：血浆TIMP-1和MMP-9在胶质瘤患者中比正常人明显升高（TIMP-1：p<0.001;MMP-9:p=0.007)。血浆TIMP-1随肿瘤级别升高而升高。血浆TIMP-1高的四级胶质瘤患者预后好于低TIMP-1的患者（Cox回归分析,HR=0.550,95%CI0.101-1.000,p=0.036）。血浆MMP-9与肿瘤级别或患者预后均无明显相关。结论：血浆TIMP-1水平与胶质瘤患者的诊断和预后相关。它的临床应用前景优于血浆MMP-9。需要进一步扩大样本研究其临床意义。

Plasma level of tissue inhibitor of matrix metalloproteinase-1 correlate with diagnosis and prognosis of glioma patients

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, 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 immune sorbent assay. Plasma TIMP-1 was compared between normal and glioma patients, between patients with different pathological grades, and between patients with different prognosis. Longitudinal changes of plasma TIMP-1 during treatment were also evaluated. Plasma 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 (HR: 0.550, 95%CI: 0.101-1.000, P=0.036). In grade IV gliomas, patients with higher plasma TIMP-1 have significantly longer survival time than those with lower plasma TIMP-1 level (25.23 months 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.