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

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

Shunsuke Yamanishi  1 , Hiroaki Nagashima  2 , Kazuhiro Tanaka  1 , Takiko Uno  1 , Yusuke Ikeuchi  1 , Hirofumi Iwahashi  1 , Mitsuru Hashiguchi  1 , Shintaro Horii  3 , Tomoo Itoh  4 , Yoshihiro Muragaki  5 , Takashi Sasayama  1
Affiliations

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

Shunsuke Yamanishi et al. J Neurooncol. 2025 Jan.

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.

Keywords: CD163; Cerebrospinal fluid; Isocitrate dehydrogenase wild-type glioblastoma; M2 macrophages; Seizure.

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Conflict of interest statement

Declarations. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the ethics review board of Kobe University (B230181). Consent to participate: Informed consent was obtained from all individual participants included in the study. Previous presentations: We declare that this work has not been published previously or submitted elsewhere for review. Competing interests: The authors declare no competing interests.

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