多体素磁共振波谱术可识别高级别胶质瘤中癌干细胞样细胞的富集灶。

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

作者信息

He Tao, Qiu Tianming, Wang Xiaodong, Gui Hongxing, Wang Xilong, Hu Qikuan, Xia Hechun, Qi Gaoyang, Wu Jinsong, Ma Hui

机构信息

Clinical Medicine College, Ningxia Medical University; Department of Neurosurgery, General Hospital of Ningxia Medical University; Ningxia Key Laboratory of Cerebrocranial Diseases, The National Key Laboratory Incubation Base, Yinchuan.

Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai.

出版信息

Onco Targets Ther. 2017 Jan 4;10:195-203. doi: 10.2147/OTT.S118834. eCollection 2017.

DOI:10.2147/OTT.S118834

PMID:28115854

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5221654/

Abstract

OBJECTIVE

This study investigated the correlation between choline/creatine (Cho/Cr) ratios determined by multivoxel proton magnetic resonance spectroscopy (H-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 H-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, <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 <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 <0.001). The protein expression levels of CD133 and nestin were highly correlated with Cho/Cr ratios (=0.897 and =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.

摘要

目的

本研究调查了多体素质子磁共振波谱（H-MRS）测定的胆碱/肌酸（Cho/Cr）比值与高级别胶质瘤中癌症干细胞样细胞（CSLCs）分布之间的相关性。

患者与方法

招募了16例高级别胶质瘤患者，术前进行H-MRS检查，以确定具有不同Cho/Cr比值的不同肿瘤区域。使用术中神经导航，从每个肿瘤内Cho/Cr比值高和低的区域准确采集肿瘤组织。通过神经球培养、免疫组织化学和蛋白质印迹法对来自不同Cho/Cr比值的胶质瘤组织区域样本中的CSLCs分布进行定量分析。

结果

与Cho/Cr比值低的组织相比，Cho/Cr比值高的组织中神经球形成率显著增加（每100个细胞中分别为13.94±5.94个和8.04±3.99个，<0.001）。免疫组织化学表明，与Cho/Cr比值低的组织样本相比，Cho/Cr比值高的组织中CD133、巢蛋白和CD15的表达升高（分别为23.6%±3.8%对18.3%±3.3%、25.2%±4.5%对19.8%±2.8%、24.5%±3.8%对17.8%±2.2%；均<0.001）。蛋白质印迹法表明，Cho/Cr比值高的区域中CD133和巢蛋白的相对蛋白表达显著高于Cho/Cr比值低的组织样本（分别为0.50±0.17对0.30±0.08、0.45±0.13对0.27±0.07；均<0.001）。CD133和巢蛋白的蛋白表达水平与Cho/Cr比值高度相关（分别为=0.897和=0.861）。