2. Academic Validation
  3. Aberrant PLAC8 expression characterizes glioblastoma with temozolomide resistance and an immunosuppressive microenvironment

Aberrant PLAC8 expression characterizes glioblastoma with temozolomide resistance and an immunosuppressive microenvironment

  • Cancer Lett. 2025 Aug 10:625:217805. doi: 10.1016/j.canlet.2025.217805.
Han She 1,  Tian-Ran Li 2,  Guozhi Zhao 3,  Liang Yi 4,  Qing Liu 2,  Zheng-Chao Liu 1,  Hao-Yu Pei 1,  Xunjia Li 5,  Deyu Zuo 6,  Qingxiang Mao 7,  Yong Li 8
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, 400042, China.
  • 2 Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China.
  • 3 Department of Urology Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
  • 4 Department of Neurosurgery, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, 400042, China.
  • 5 Department of Nephrology, The First Affiliated Hospital of Chongqing University of Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400021, China.
  • 6 Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing University of Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400021, China; Department of Research and Development, Chongqing Precision Medical Industry Technology Research Institute, Chongqing, 400000, China. Electronic address: zuodeyu@cqctcm.edu.cn.
  • 7 Department of Anesthesiology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, 400042, China. Electronic address: qxmao@tmmu.edu.cn.
  • 8 Department of Anesthesiology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, 400042, China. Electronic address: leo_1115@tmmu.edu.cn.
PMID: 40398706 DOI: 10.1016/j.canlet.2025.217805
Abstract

Glioblastoma (GBM), Isocitrate Dehydrogenase-wildtype (IDH-WT) represents the most prevalent and clinically aggressive subtype of adult diffuse gliomas, typically associated with poor prognosis. Temozolomide (TMZ) remains the first-line chemotherapeutic agent for GBM; however, the emergence of TMZ resistance represents a major therapeutic obstacle in clinical practice. This study identifies placenta-specific 8 (PLAC8) as a novel mediator of TMZ resistance in IDH-WT GBM. Elevated PLAC8 expression was strongly correlated with poorer survival rates, higher tumor grades in glioma, establishing it as an independent prognostic factor. Notably, consistent upregulation of PLAC8 was observed in both TMZ-resistant GBM cells and TMZ-treated patients, suggesting its potential as a biomarker for TMZ resistance. Mechanistic studies revealed that PLAC8 regulates TMZ sensitivity in GBM cells through the AKT-mTOR signaling pathway. Additionally, integrated bioinformatics and clinical analyses demonstrated that PLAC8 expression positively correlates with immune cell infiltration while promoting an immunosuppressive tumor microenvironment and modulating immunotherapy-related biomarkers, suggesting its potential as a predictive biomarker for immunotherapy response. In conclusion, PLAC8 represents a promising biomarker and therapeutic target for overcoming TMZ resistance and guiding immunotherapy in GBM. This study provides valuable insights for the development of personalized treatment strategies aimed at improving patient outcomes.

Keywords

Glioblastoma; Immune infiltration; Immunotherapy; PLAC8; TMZ resistance.

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