NMR Surgical Laboratory, Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, USA.
Int J Oncol. 2010 Feb;36(2):301-6. doi: 10.3892/ijo_00000500.
The non-essential amino acid neurotransmitter glycine (Gly) may serve as a biomarker for brain tumors. Using 36 biopsies from patients with brain tumors [12 glioblastoma multiforme (GBM); 10 low-grade (LG), including 7 schwannoma and 3 pylocytic astrocytoma; 7 meningioma (MN); 7 brain metastases (MT), including 3 adenocarcinoma and 4 breast cancer] and 9 control biopsies from patients undergoing surgery for epilepsy, we tested the hypothesis that the presence of glycine may distinguish among these brain tumor types. Using high-resolution magic angle spinning (HRMAS) 1H magnetic resonance spectroscopy (MRS), we determined a theoretically optimum echo time (TE) of 50 ms for distinguishing Gly signals from overlapping myo-inositol (Myo) signals and tested our methodology in phantom and biopsy specimens. Quantitative analysis revealed higher levels of Gly in tumor biopsies (all combined) relative to controls; Gly levels were significantly elevated in LG, MT and GBM biopsies (P<or=0.05). Residual Myo levels were elevated in LG and MT and reduced in MN and GBM (P<0.05 vs. control levels). We observed higher levels of Gly in GBM as compared to LG tumors (P=0.05). Meanwhile, although Gly levels in GBM and MT did not differ significantly from each other, the Gly:Myo ratio did distinguish GBM from MT (P<0.003) and from all other groups, a distinction that has not been adequately made previously. We conclude from these findings that Gly can serve as a biomarker for brain tumors and that the Gly:Myo ratio may be a useful index for brain tumor classification.
非必需氨基酸神经递质甘氨酸(Gly)可能是脑肿瘤的生物标志物。我们使用了 36 个脑肿瘤患者的活检样本(12 个多形性胶质母细胞瘤(GBM);10 个低级别肿瘤,包括 7 个神经鞘瘤和 3 个毛细胞星形细胞瘤;7 个脑膜瘤(MN);7 个脑转移瘤(MT),包括 3 个腺癌和 4 个乳腺癌)和 9 个因癫痫接受手术的患者的对照活检样本,以验证甘氨酸的存在是否可以区分这些脑肿瘤类型的假设。我们使用高分辨率魔角旋转(HRMAS)1H 磁共振波谱(MRS),确定了区分 Gly 信号与重叠肌醇(Myo)信号的理论最佳回波时间(TE)为 50ms,并在幻影和活检标本中测试了我们的方法。定量分析显示肿瘤活检样本中的 Gly 水平相对对照样本更高;低级别肿瘤、MT 和 GBM 活检样本中的 Gly 水平显著升高(P<0.05)。LG 和 MT 中的残留 Myo 水平升高,而 MN 和 GBM 中的残留 Myo 水平降低(P<0.05 与对照水平相比)。我们观察到 GBM 中的 Gly 水平高于 LG 肿瘤(P=0.05)。同时,尽管 GBM 和 MT 中的 Gly 水平彼此之间没有显著差异,但 Gly:Myo 比值可以区分 GBM 和 MT(P<0.003),以及与所有其他组的区分,这一点以前没有得到充分的区分。我们从这些发现中得出结论,Gly 可以作为脑肿瘤的生物标志物,并且 Gly:Myo 比值可能是脑肿瘤分类的有用指标。