Wilson Martin, Gill Simrandip K, MacPherson Lesley, English Martin, Arvanitis Theodoros N, Peet Andrew C
School of Cancer Sciences, University of Birmingham, Birmingham; Birmingham Children's Hospital NHS Foundation Trust, Birmingham; and
School of Cancer Sciences, University of Birmingham, Birmingham; Birmingham Children's Hospital NHS Foundation Trust, Birmingham; and.
Clin Cancer Res. 2014 Sep 1;20(17):4532-9. doi: 10.1158/1078-0432.CCR-13-2320. Epub 2014 Jun 19.
Medulloblastoma is the most common malignant brain tumor occurring in childhood and is a significant cause of morbidity and mortality in pediatric oncology. More intense treatment strategies are recommended for patients displaying high-risk factors; however, considerable variation in outcome remains, indicating a need for improved predictive markers. In this study, 1H magnetic resonance spectroscopy (MRS) was used to investigate noninvasive molecular biomarkers of survival in medulloblastoma.
MRS was performed on a series of 35 biopsy-confirmed medulloblastoma cases. One case was excluded because of poor quality MRS. The prognostic value of MRS detectable biomarkers was investigated using Cox regression, retrospectively (N=15). A subsequent validation analysis (N=19) was also performed to reduce the chance of type I errors. Where available, high-resolution ex vivo MRS of biopsy tissue was used to confirm biomarker assignments.
The retrospective analysis revealed that creatine, glutamate, and glycine were markers of survival (P<0.01). The validation analysis showed that glutamate was a robust marker, with a hazard ration (HR) of 8.0 for the full dataset (P=0.0003, N=34). A good correlation between in vivo and ex vivo MRS glutamate/total-choline was found (P=0.001), validating the in vivo assignment. Ex vivo glutamate/total-choline was also associated with survival (P<0.01).
The identification of glutamate as a predictive biomarker of survival in pediatric medulloblastoma provides a clinically viable risk factor and highlights the importance of more detailed studies into the metabolism of this disease. Noninvasive biomarker detection using MRS may offer improved disease monitoring and potential for widespread use following multicenter validation.
髓母细胞瘤是儿童期最常见的恶性脑肿瘤，也是儿科肿瘤学中发病和死亡的重要原因。对于显示出高危因素的患者，建议采用更强化的治疗策略；然而，结果仍存在相当大的差异，这表明需要改进预测标志物。在本研究中，采用氢磁共振波谱（MRS）来研究髓母细胞瘤生存的非侵入性分子生物标志物。
对一系列35例经活检证实的髓母细胞瘤病例进行了MRS检查。1例因MRS质量差而被排除。使用Cox回归对MRS可检测生物标志物的预后价值进行回顾性研究（N = 15）。随后还进行了验证分析（N = 19）以减少I型错误的可能性。在可行的情况下，使用活检组织的高分辨率离体MRS来确认生物标志物的归属。
回顾性分析显示，肌酸、谷氨酸和甘氨酸是生存标志物（P < 0.01）。验证分析表明，谷氨酸是一个可靠的标志物，整个数据集的风险比（HR）为8.0（P = 0.0003，N = 34）。发现体内和离体MRS谷氨酸/总胆碱之间具有良好的相关性（P = 0.001），验证了体内归属。离体谷氨酸/总胆碱也与生存相关（P < 0.01）。
谷氨酸作为小儿髓母细胞瘤生存的预测生物标志物的鉴定提供了一个临床上可行的危险因素，并突出了对该疾病代谢进行更详细研究的重要性。使用MRS进行非侵入性生物标志物检测可能会改善疾病监测，并在多中心验证后具有广泛应用的潜力。
