胶质瘤，特别是胶质母细胞瘤（GBM），由于其侵袭性和预后不良而带来重大挑战。通过生物标志物进行早期检测对于改善结果至关重要。本研究旨在利用手性氨基酸分析来鉴定神经胶质瘤（特别是 GBM）的新型生物标志物。我们使用手性氨基酸分析来测量 33 名原发性神经胶质瘤患者和 24 名健康志愿者的切除组织（肿瘤和非肿瘤）、血液和尿液中的氨基酸 L 型和 D 型异构体水平。通过评估 D-氨基酸氧化酶（DAO）（一种 D-氨基酸降解酶）的水平来研究脑组织中的 D-氨基酸代谢。 GBM小鼠模型是通过将GBM细胞移植到大脑中来创建的，以确认神经胶质瘤是否影响血液和尿液的手性氨基酸谱。我们还评估了 GBM 细胞产生的 D-氨基酸是否参与细胞增殖。与非神经胶质瘤组织相比，神经胶质瘤组织中的 D-天冬酰胺 (D-Asn) 水平较高，DAO 表达较低。 GBM 患者的血液和尿液 D-Asn 水平低于健康志愿者 (p<0.001)，GBM 切除后则升高 (p<0.05)。健康志愿者和 GBM 患者的尿液 D-Asn 水平存在差异（曲线下面积：0.93，敏感性：0.88，特异性：0.92）。 GBM 小鼠模型验证了 GBM 中尿 D-Asn 的减少。 GBM 细胞使用 D-Asn 进行细胞增殖。神经胶质瘤会引起手性氨基酸谱的改变，影响血液和尿液的水平。尿 D-Asn 成为一种有前途的神经胶质瘤诊断生物标志物，反映肿瘤的存在和严重程度。© 2024。作者。

Gliomas, particularly glioblastomas (GBMs), pose significant challenges due to their aggressiveness and poor prognosis. Early detection through biomarkers is critical for improving outcomes. This study aimed to identify novel biomarkers for gliomas, particularly GBMs, using chiral amino acid profiling. We used chiral amino acid analysis to measure amino acid L- and D-isomer levels in resected tissues (tumor and non-tumor), blood, and urine from 33 patients with primary gliomas and 24 healthy volunteers. The levels of D-amino acid oxidase (DAO), a D-amino acid-degrading enzyme, were evaluated to investigate the D-amino acid metabolism in brain tissue. The GBM mouse model was created by transplanting GBM cells into the brain to confirm whether gliomas affect blood and urine chiral amino acid profiles. We also assessed whether D-amino acids produced by GBM cells are involved in cell proliferation. D-asparagine (D-Asn) levels were higher and DAO expression was lower in glioma than in non-glioma tissues. Blood and urinary D-Asn levels were lower in patients with GBM than in healthy volunteers (p < 0.001), increasing after GBM removal (p < 0.05). Urinary D-Asn levels differentiated between healthy volunteers and patients with GBM (area under the curve: 0.93, sensitivity: 0.88, specificity: 0.92). GBM mouse model validated the decrease of urinary D-Asn in GBM. GBM cells used D-Asn for cell proliferation. Gliomas induce alterations in chiral amino acid profiles, affecting blood and urine levels. Urinary D-Asn emerges as a promising diagnostic biomarker for gliomas, reflecting tumor presence and severity.© 2024. The Author(s).