YKL-40 and matrix metalloproteinase-9 as potential serum biomarkers for patients with high-grade gliomas

YKL-40 and matrix metalloproteinase-9 as potential serum biomarkers for patients with high-grade gliomas
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DOI:
10.1158/1078-0432.ccr-06-0181
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发表时间:
2006-10-01
影响因子:
11.5
通讯作者:
Holland, Eric C.
Holland, Eric C.
中科院分区:
医学1区
文献类型:
--
作者:
Hormigo, Adilia;Gu, Bin;Holland, Eric C.

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目的:生物标志物可以帮助诊断,监测治疗反应,并评估一些癌症患者的预后。YKL-40和基质金属蛋白酶-9(MMP-9)是恶性胶质瘤中高度差异表达的两种蛋白质。我们获得了前瞻性的纵向血清样本与胶质瘤患者,以确定是否YKL-40或MMP-9可以被用作血清marker. Experimental Design:血清样本同时获得磁共振成像扫描。ELISA法测定YKL-40和MMP-9的值与患者的放射学状态和survival.Results:高级别胶质瘤患者谁接受了手术切除肿瘤有短暂的增加,在术后期间的YKL-40和MMP-9血清水平。没有放射学疾病证据的多形性胶质母细胞瘤(GBM)患者(n = 10例患者,50个样本)的YKL-40和MMP-9水平显著低于活动性肿瘤患者(n = 66例患者,209个样本; P = 0.0003和0.0002,分别)。无放射学疾病证据的间变性胶质瘤患者(n = 32例患者,107个样本)与活动性肿瘤患者(n = 48例患者,199个样本; P = 0.04)相比,YKL-40水平也显著较低。YKL-40与GBM、间变性星形细胞瘤患者的生存率呈显著负相关(危险比为1.4,P = 0.02),与间变性星形细胞瘤患者的生存率呈显著负相关(危险比为2.2,P = 0.05)。结论:YKL-40和MMP-9可在患者血清中监测,有助于确认GBM和间变性胶质瘤患者中不存在活动性疾病。YKL-40可作为高级别胶质瘤患者生存期的预测因子。需要更大患者人群的纵向研究来证实这些发现。
Purpose: Biomarkers can facilitate diagnosis, monitor treatment response, and assess prognosis in some patients with cancer. YKL-40 and matrix metalloproteinase-9 (MMP-9) are two proteins highly differentially expressed by malignant gliomas. We obtained prospective longitudinal serum samples from patients with gliomas to determine whether YKL-40 or MMP-9 could be used as serum markers.Experimental Design: Serum samples were obtained concurrently with magnetic resonance imaging scans. YKL-40 and MMP-9 were determined by ELISA and the values correlated with the patient's radiographic status and survival.Results: High-grade glioma patients who underwent a surgical resection of their tumor had transient increase of both YKL-40 and MMP-9 serum levels in the postoperative period. Glioblastoma multiforme (GBM) patients with no radiographic evidence of disease (n = 10 patients, 50 samples) had a significantly lower level of YKL-40 and MMP-9 than patients with active tumor (n = 66 patients, 209 samples; P = 0.0003 and 0.0002, respectively). Anaplastic glioma patients with no radiographic evidence of disease (n = 32 patients, 107 samples) also had a significantly lower level of YKL-40 compared with those patients with active tumor (n = 48 patients, 199 samples; P = 0.04). There was a significant inverse association between YKL-40 and survival in GBM, hazard ratio (hazard ratio, 1.4; P = 0.02), and anaplastic astrocytoma patients (hazard ratio, 2.2; P = 0.05).Conclusions: YKL-40 and MMP-9 can be monitored in patients' serum and help confirm the absence of active disease in GBM and YKL-40 in anaplastic glioma patients. YKL-40 can be used as predictor of survival in patients with high-grade glioma. Longitudinal studies with a larger patient population are needed to confirm these findings.