神经胶质瘤中的氨基酸代谢:体内 MR 光谱检测丙氨酸作为神经胶质瘤患者生存不良的潜在生物标志物。
Amino acid metabolism in glioma: in vivo MR-spectroscopic detection of alanine as a potential biomarker of poor survival in glioma patients.
发表日期:2024 Aug 27
作者:
Seyma Alcicek, Ulrich Pilatus, Andrei Manzhurtsev, Katharina J Weber, Michael W Ronellenfitsch, Joachim P Steinbach, Elke Hattingen, Katharina J Wenger
来源:
Brain Structure & Function
摘要:
氨基酸代谢的重编程与启动和促进肿瘤的形成和生长有关。因此,人们对针对氨基酸代谢的抗癌疗法越来越感兴趣。在开发神经胶质瘤的个性化治疗方法时,体内质子磁共振波谱(MRS)是非侵入性监测肿瘤代谢的宝贵工具。在这里,我们评估了 MRS 检测到的脑氨基酸和肌醇作为神经胶质瘤的潜在诊断和预后生物标志物。我们使用短回波和长回波测量了 38 名 MRI 疑似神经胶质瘤患者的丙氨酸、甘氨酸、谷氨酸、谷氨酰胺和肌醇。 -时间单体素 PRESS MRS 序列。根据患者的 IDH 突变状态、CNS WHO 分级和总生存期评估丙氨酸、甘氨酸和肌醇的可检测性以及(谷氨酸 谷氨酰胺)/总肌酸比值。 -肌醇与IDH野生型(分别为p = 0.0008,p = 0.007)和WHO 4级(分别为p = 0.01,p = 0.04)显着相关,甘氨酸检测与两者均不显着相关。 WHO 4级中(谷氨酸 谷氨酰胺)/总肌酸的比率显着高于2级和3级。我们发现丙氨酸检测的胶质瘤患者的总生存期显着缩短(p = 0.00002)。关注MRS中的氨基酸可以提高其对胶质瘤的诊断和预后价值。即使存在脂质,丙氨酸在长 TE 时也可见,可能是总体生存的相关指标。© 2024。作者。
Reprogramming of amino acid metabolism is relevant for initiating and fueling tumor formation and growth. Therefore, there has been growing interest in anticancer therapies targeting amino acid metabolism. While developing personalized therapeutic approaches to glioma, in vivo proton magnetic resonance spectroscopy (MRS) is a valuable tool for non-invasive monitoring of tumor metabolism. Here, we evaluated MRS-detected brain amino acids and myo-inositol as potential diagnostic and prognostic biomarkers in glioma.We measured alanine, glycine, glutamate, glutamine, and myo-inositol in 38 patients with MRI-suspected glioma using short and long echo-time single-voxel PRESS MRS sequences. The detectability of alanine, glycine, and myo-inositol and the (glutamate + glutamine)/total creatine ratio were evaluated against the patients' IDH mutation status, CNS WHO grade, and overall survival.While the detection of alanine and non-detection of myo-inositol significantly correlated with IDH wildtype (p = 0.0008, p = 0.007, respectively) and WHO grade 4 (p = 0.01, p = 0.04, respectively), glycine detection was not significantly associated with either. The ratio of (glutamate + glutamine)/total creatine was significantly higher in WHO grade 4 than in 2 and 3. We found that the overall survival was significantly shorter in glioma patients with alanine detection (p = 0.00002).Focusing on amino acids in MRS can improve its diagnostic and prognostic value in glioma. Alanine, which is visible at long TE even in the presence of lipids, could be a relevant indicator for overall survival.© 2024. The Author(s).