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Peer-reviewedCC BY-NC-NDCancer cell international

Quantitative proteomic landscape reveals the role of CSPG5 in the recurrence of glioma.

1 more authors
9 affiliations
  1. 1The School of Medicine, Nankai University, 94 Weijin Road, Tianjin, 300071, China.
  2. 2Department of Neurosurgery, Fourth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China.
  3. 3Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
  4. 4Department of Laboratory Medicine, the First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.
  5. 5Department of Pathology, the First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.
  6. 6The Second Surgical Department of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
  7. 7State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, China.
  8. 8The School of Medicine, Nankai University, 94 Weijin Road, Tianjin, 300071, China. [email protected].
  9. 9The School of Medicine, Nankai University, 94 Weijin Road, Tianjin, 300071, China. [email protected].

Abstract

Background

The high recurrence rate of glioma accounts for the majority of glioma-related deaths. Although numerous studies have investigated genomic and transcriptomic alterations, high-resolution quantitative proteomic profiling studies remain limited.Methods

A total of 63 pairs of primary and recurrent formalin-fixed paraffin-embedded glioma tissues (WHO grade II-IV) were collected. Proteomic profiles were generated by data-independent acquisition mass spectrometry (DIA-MS). Differentially expressed proteins were validated using publicly available databases, immunohistochemistry, and Western blotting. The effects of CSPG5 on glioma cell proliferation and invasion were assessed in vitro and in an orthotopic mouse model. Protein-protein interactions were examined by co-immunoprecipitation, and the influence of CSPG5 on ErbB2 degradation was evaluated by immunofluorescence and quantitative PCR.Results

Two distinct proteomic clusters (Cluster 1 and Cluster 2) associated with glioma recurrence were identified. Chondroitin sulfate proteoglycan 5 (CSPG5) was markedly down-regulated in recurrent tumors. Overexpression of CSPG5 significantly inhibited glioma cell proliferation and invasion in vitro and reduced tumor burden in vivo. Mechanistically, CSPG5 interacted with ErbB2 and promoted its lysosomal degradation, leading to attenuated PI3K-AKT and ERK signaling.Conclusions

CSPG5 acts as a novel suppressor of ErbB2 signaling; its loss facilitates ErbB2 hyperactivation and thereby promotes glioma recurrence.

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BibTeX
@article{wang2026quantitative,
  title = {{Quantitative proteomic landscape reveals the role of CSPG5 in the recurrence of glioma.}},
  author = {Shijian Wang and Baorui Tian and Huimin Liu and Chen Zhang and Jianan Wang and Xin Song and Ruibing Li and Haoran Guo and Nan Wang and Wanjun Zhang and Yongjun Piao and Yi Shi and Rong Xiang},
  journal = {Cancer cell international},
  year = {2026},
  month = jul,
  doi = {10.1186/s12935-026-04430-z},
  url = {https://europepmc.org/article/MED/42897630},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Quantitative proteomic landscape reveals the role of CSPG5 in the recurrence of glioma.
AU  - Shijian Wang
AU  - Baorui Tian
AU  - Huimin Liu
AU  - Chen Zhang
AU  - Jianan Wang
AU  - Xin Song
AU  - Ruibing Li
AU  - Haoran Guo
AU  - Nan Wang
AU  - Wanjun Zhang
AU  - Yongjun Piao
AU  - Yi Shi
AU  - Rong Xiang
PY  - 2026
DA  - 2026/07/01
JO  - Cancer cell international
DO  - 10.1186/s12935-026-04430-z
UR  - https://europepmc.org/article/MED/42897630
AB  - Background  The high recurrence rate of glioma accounts for the majority of glioma-related deaths. Although numerous studies have investigated genomic and transcriptomic alterations, high-resolution quantitative proteomic profiling studies remain limited.Methods  A total of 63 pairs of primary and recurrent formalin-fixed paraffin-embedded glioma tissues (WHO grade II-IV) were collected. Proteomic profiles were generated by data-independent acquisition mass spectrometry (DIA-MS). Differentially expressed proteins were validated using publicly available databases, immunohistochemistry, and Western blotting. The effects of CSPG5 on glioma cell proliferation and invasion were assessed in vitro and in an orthotopic mouse model. Protein-protein interactions were examined by co-immunoprecipitation, and the influence of CSPG5 on ErbB2 degradation was evaluated by immunofluorescence and quantitative PCR.Results  Two distinct proteomic clusters (Cluster 1 and Cluster 2) associated with glioma recurrence were identified. Chondroitin sulfate proteoglycan 5 (CSPG5) was markedly down-regulated in recurrent tumors. Overexpression of CSPG5 significantly inhibited glioma cell proliferation and invasion in vitro and reduced tumor burden in vivo. Mechanistically, CSPG5 interacted with ErbB2 and promoted its lysosomal degradation, leading to attenuated PI3K-AKT and ERK signaling.Conclusions  CSPG5 acts as a novel suppressor of ErbB2 signaling; its loss facilitates ErbB2 hyperactivation and thereby promotes glioma recurrence.
SN  - 1475-2867
ER  -