Hormigo Adília, Gu Bin, Karimi Sasan, Riedel Elyn, Panageas Katherine S, Edgar Mark A, Tanwar Meena K, Rao Jasti S, Fleisher Martin, DeAngelis Lisa M, Holland Eric C
Clinical Laboratories, Neurosurgical Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Clin Cancer Res. 2006 Oct 1;12(19):5698-704. doi: 10.1158/1078-0432.CCR-06-0181.
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.
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.
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).
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.
生物标志物有助于某些癌症患者的诊断、监测治疗反应及评估预后。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。我们获取了胶质瘤患者的前瞻性纵向血清样本，以确定YKL-40或MMP-9是否可用作血清标志物。
血清样本与磁共振成像扫描同时获取。通过酶联免疫吸附测定法（ELISA）测定YKL-40和MMP-9，并将其值与患者的影像学状态及生存情况相关联。
接受肿瘤手术切除的高级别胶质瘤患者在术后YKL-40和MMP-9血清水平均有短暂升高。影像学无疾病证据的多形性胶质母细胞瘤（GBM）患者（n = 10例患者，50份样本）的YKL-40和MMP-9水平显著低于有活动性肿瘤的患者（n = 66例患者，209份样本；P分别为0.0003和0.0002）。影像学无疾病证据的间变性胶质瘤患者（n = 32例患者，107份样本）的YKL-40水平也显著低于有活动性肿瘤的患者（n = 48例患者，199份样本；P = 0.04）。在GBM患者中，YKL-40与生存之间存在显著负相关，风险比（风险比，1.4；P = 0.02），在间变性星形细胞瘤患者中也是如此（风险比，2.2；P = 0.05）。
可在患者血清中监测YKL-40和MMP-9，有助于确认GBM患者无活动性疾病以及间变性胶质瘤患者无YKL-40。YKL-40可作为高级别胶质瘤患者生存的预测指标。需要对更多患者进行纵向研究以证实这些发现。
