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术前癫痫发作与异柠檬酸脱氢酶野生型胶质母细胞瘤脑脊液中M2巨噬细胞标志物可溶性CD163表达降低之间的关联。

Association of preoperative seizures with reduced expression of soluble CD163, an M2 macrophage marker, in the cerebrospinal fluid in isocitrate dehydrogenase wild-type glioblastoma.

作者信息

Yamanishi Shunsuke, Nagashima Hiroaki, Tanaka Kazuhiro, Uno Takiko, Ikeuchi Yusuke, Iwahashi Hirofumi, Hashiguchi Mitsuru, Horii Shintaro, Itoh Tomoo, Muragaki Yoshihiro, Sasayama Takashi

机构信息

Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

Division of Radiology, Department of Medical Technology, Kobe University Hospital, Kobe, Japan.

出版信息

J Neurooncol. 2025 Jan;171(1):95-103. doi: 10.1007/s11060-024-04837-6. Epub 2024 Oct 8.

Abstract

PURPOSE

To investigate the relationship between the tumor microenvironment (TME), tumor-related seizures (TRS), and cerebrospinal fluid (CSF) markers that predict preoperative seizures in patients with glioblastoma.

METHODS

In total, 47 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma who underwent preoperative CSF examination, 3-T magnetic resonance spectroscopy (MRS), and neurological surgery between January 2017 and December 2023 were included. We measured the concentrations of soluble CD163 (sCD163), a soluble form of the M2 macrophage marker, in the CSF, the metabolite concentration on MRS, and the number of CD163-positive M2 macrophages in the tumor tissue. Factors associated with preoperative seizures were examined.

RESULTS

Twelve patients (25.5%) had preoperative seizures. sCD163 levels in the CSF were positively correlated with the number of CD163-positive M2 macrophages in the tumor tissue, and both were significantly lower in the preoperative seizure group than in the non-preoperative seizure group (p = 0.0124 and p < 0.0001, respectively). MRS indicated that only glutathione (GSH) concentrations were higher in the preoperative seizure group than in the non-preoperative seizure group (2.55 mM and 1.87 mM, respectively; p = 0.0171). CD163-positive M2 macrophages were inversely correlated with GSH levels. sCD163 in the CSF had a high predictive accuracy (sensitivity, 91.7%; specificity, 54.3%; and area under the receiver operator curve, 0.745) for preoperative seizures.

CONCLUSIONS

The CSF level of sCD163 is useful for predicting the TME and preoperative seizures in IDH wild-type glioblastoma.

摘要

目的

探讨肿瘤微环境(TME)、肿瘤相关性癫痫(TRS)以及预测胶质母细胞瘤患者术前癫痫发作的脑脊液(CSF)标志物之间的关系。

方法

纳入2017年1月至2023年12月期间接受术前脑脊液检查、3-T磁共振波谱(MRS)和神经外科手术的47例异柠檬酸脱氢酶(IDH)野生型胶质母细胞瘤患者。我们测量了脑脊液中M2巨噬细胞标志物的可溶性形式可溶性CD163(sCD163)的浓度、MRS上的代谢物浓度以及肿瘤组织中CD163阳性M2巨噬细胞的数量。研究了与术前癫痫发作相关的因素。

结果

12例患者(25.5%)有术前癫痫发作。脑脊液中sCD163水平与肿瘤组织中CD163阳性M2巨噬细胞数量呈正相关,且术前癫痫发作组两者均显著低于非术前癫痫发作组(分别为p = 0.0124和p < 0.0001)。MRS显示,仅术前癫痫发作组的谷胱甘肽(GSH)浓度高于非术前癫痫发作组(分别为2.55 mM和1.87 mM;p = 0.0171)。CD163阳性M2巨噬细胞与GSH水平呈负相关。脑脊液中的sCD163对术前癫痫发作具有较高的预测准确性(敏感性为91.7%;特异性为54.3%;受试者操作特征曲线下面积为0.745)。

结论

sCD163的脑脊液水平有助于预测IDH野生型胶质母细胞瘤的TME和术前癫痫发作。

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