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Noninvasive detection of glutamate predicts survival in pediatric medulloblastoma
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Wilson, Martin, Gill, S. K., MacPherson, L., English, M., Arvanitis, Theodoros N. and Peet, A. C. (2014) Noninvasive detection of glutamate predicts survival in pediatric medulloblastoma. Clinical Cancer Research, Volume 20 (Number 17). pp. 4532-4539. doi:10.1158/1078-0432.CCR-13-2320 ISSN 1078-0432.
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Official URL: http://dx.doi.org/10.1158/1078-0432.CCR-13-2320
Abstract
Purpose: 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.
Experimental Design: 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.
Results: 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).
Conclusion: 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.
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Engineering > WMG (Formerly the Warwick Manufacturing Group) | ||||
Journal or Publication Title: | Clinical Cancer Research | ||||
Publisher: | American Association for Cancer Research | ||||
ISSN: | 1078-0432 | ||||
Official Date: | 1 September 2014 | ||||
Dates: |
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Volume: | Volume 20 | ||||
Number: | Number 17 | ||||
Page Range: | pp. 4532-4539 | ||||
DOI: | 10.1158/1078-0432.CCR-13-2320 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
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