ORIGINAL RESEARCH article

Front. Oncol.

Sec. Pharmacology of Anti-Cancer Drugs

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1554845

This article is part of the Research TopicClonal Heterogeneity and Tumor Evolution: Implications for Cancer TherapyView all articles

Interrogation of Macrophage-Related Prognostic Signatures Reveals a Potential Immune-Mediated Therapy Strategy by Histone Deacetylase Inhibition in Glioma

Provisionally accepted
Xisen WangXisen Wang1,2Xuya WangXuya Wang2Lei ChenLei Chen3,4Jikang FanJikang Fan5Jianshen LiangJianshen Liang2Yu ZhangYu Zhang3Yiming ZhangYiming Zhang2Yaohua LiYaohua Li3Shengping YuShengping Yu3Chen ZhangChen Zhang3Tao LiTao Li3*Xuejun YangXuejun Yang2*
  • 1Tianjin Medical University General Hospital, Tianjin, China
  • 2Department of Neurosurgery, Beijing Tsinghua Changgeng Hospital, Tsinghua University, Beijing, China
  • 3Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, Tianjin Municipality, China
  • 4Department of Neurosurgery, Tianjin First Central Hospital, Tianjin, China
  • 5Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, China

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Glioma-associated macrophages (GAMs) originate from intracranially resident microglia and myeloid-derived macrophages. In the glioma microenvironment, these two types of macrophages tend to adopt a specialized activation state known as type 2 or M2 macrophages and play crucial roles in the progression of glioma. To identify various genes associated with GAMs, we took the intersection between the genes identified as for GAMs using single-cell RNA sequencing (scRNAseq) data and the genes identified as M2 macrophage module genes through weighted gene coexpression network analysis (WGCNA). 14 prognostic genes (TREM2, GAL3ST4, AP1B1, SLA, CYBB, CD53, SLC37A2, ABI3, RIN3, SCIN, SIGLEC10, C3, PLEKHO2, and PLXDC2) were screened using various regression methods, including univariate cox regression, multivariate cox regression, and least absolute shrinkage and selection operator (LASSO) regression analysis from GAMs-associated genes. These genes were utilized in the construction validation of prognostic signatures, as well as to unveil the immune landscape. During the drug screening, Vorinostat demonstrated the highest risk score and the lowest half-maximal inhibitory concentration (IC50). The expression of the above 14 prognostic genes was investigated by employing the glioma cellmacrophage co-culture model, and it was demonstrated that Vorinostat exerted a significant inhibitory effect on the glioma microenvironment. These innovative findings provide valuable insight into the molecular mechanism of GAMs in glioma, reveal the immunological landscape of glioma, and aid in identification of potential treatment targets and drug mechanisms of action.

Keywords: Glioma, Glioma-associated macrophages, Prognostic signature, immune microenvironment, Histone Deacetylase Inhibitors, vorinostat

Received: 03 Jan 2025; Accepted: 16 May 2025.

Copyright: © 2025 Wang, Wang, Chen, Fan, Liang, Zhang, Zhang, Li, Yu, Zhang, Li and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Tao Li, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, Tianjin Municipality, China
Xuejun Yang, Department of Neurosurgery, Beijing Tsinghua Changgeng Hospital, Tsinghua University, Beijing, 102218, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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