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Multivoxel magnetic resonance spectroscopy identifies enriched foci of cancer stem-like cells in high-grade gliomas

Authors He T, Qiu T, Wang X, Gui H, Wang X, Hu Q, Xia H, Qi G, Wu J, Ma H

Received 3 August 2016

Accepted for publication 30 November 2016

Published 4 January 2017 Volume 2017:10 Pages 195—203

DOI https://doi.org/10.2147/OTT.S118834

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati

Tao He,1–3,* Tianming Qiu,4,* Xiaodong Wang,5 Hongxing Gui,6 Xilong Wang,2 Qikuan Hu,3,7 Hechun Xia,2 Gaoyang Qi,1,2 Jinsong Wu,4 Hui Ma2

1Clinical Medicine College, Ningxia Medical University, 2Department of Neurosurgery, General Hospital of Ningxia Medical University, 3Ningxia Key Laboratory of Cerebrocranial Diseases, The National Key Laboratory Incubation Base, Yinchuan, 4Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 5Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 6Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School of Rutgers University, Piscataway, NJ, USA; 7Department of Physiology, Ningxia Medical University, Yinchuan, People’s Republic of China

*These authors contributed equally to this work

Objective: This study investigated the correlation between choline/creatine (Cho/Cr) ratios determined by multivoxel proton magnetic resonance spectroscopy (1H-MRS) and the distribution of cancer stem-like cells (CSLCs) in high-grade gliomas.
Patients and methods: Sixteen patients with high-grade gliomas were recruited and underwent 1H-MRS examination before surgery to identify distinct tumor regions with variable Cho/Cr ratios. Using intraoperative neuronavigation, tumor tissues were accurately sampled from regions with high and low Cho/Cr ratios within each tumor. The distribution of CSLCs in samples from glioma tissue regions with different Cho/Cr ratios was quantified by neurosphere culture, immunohistochemistry, and Western blot.
Results: The mean neurosphere formation rate in tissues with high Cho/Cr ratios was significantly increased compared with that in low Cho/Cr ratio tissues (13.94±5.94 per 100 cells vs 8.04±3.99 per 100 cells, P<0.001). Immunohistochemistry indicated that tissues with high Cho/Cr ratios had elevated expression of CD133, nestin, and CD15, relative to low Cho/Cr ratio tissue samples (23.6%±3.8% vs 18.3%±3.3%, 25.2%±4.5% vs 19.8%±2.8%, 24.5%±3.8% vs 17.8%±2.2%, respectively; all P<0.001). Western blot demonstrated that relative CD133 and nestin protein expression in high Cho/Cr ratio regions was significantly higher than that in low Cho/Cr ratio tissue samples (0.50±0.17 vs 0.30±0.08, 0.45±0.13 vs 0.27±0.07, respectively; both P<0.001). The protein expression levels of CD133 and nestin were highly correlated with Cho/Cr ratios (r=0.897 and r=0.861, respectively).
Conclusion: Cho/Cr ratios correlate with the distribution of CSLCs in high-grade gliomas, and this may assist in identifying foci enriched with CSLCs and thus improve the management of high-grade gliomas.

Keywords:
high-grade glioma, 1H-MRS, cancer stem-like cells, choline, creatine, Cho/Cr

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