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Updated: May 21, 2026
Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
Network-driven prioritization and functional phenotyping nominate TTC23 as a biomarker-informed target in
Jianqiang Hao1, Hongbin Liu1, Yongqiang Ye1
1Department of Neurosurgery, Ziyang Central Hospital, West China Hospital of Sichuan University-Ziyang Hospital, Ziyang, China.
Background:
Glioblastoma (GBM) remains a lethal brain tumor with limited therapeutic options and near-universal recurrence. Drug repurposing offers a practical strategy, but pleiotropic compounds require systematic target triage to yield actionable and testable vulnerabilities.
Methods:
We integrated GBM transcriptomic dysregulation with curated chlorpromazine (CPZ)-associated targets to define drug-disease intersecting genes, constructed a protein-protein interaction network, and developed an outcome-linked Lasso-Cox prognostic model to prioritize core candidates. Structure-informed docking and coarse-grained conformational sampling were used to evaluate the plausibility of a TTC23-CPZ interaction. TTC23-associated pathway activity, oncogenic state features, and immune contexture were characterized using expression stratification, enrichment and state scoring, cancer-immunity cycle analysis, and immune infiltration estimation. Functional validation was performed in GBM cell models to assess migration, apoptosis, cell viability, and clonogenic potential under TTC23 perturbation with or without CPZ exposure.
Results:
Integrated CPZ-GBM intersection analysis and network-based prognostic modeling consistently prioritized TTC23 as a clinically relevant candidate. Structure-based analyses supported a consistent TTC23-CPZ interaction hypothesis across conformational sampling. Elevated TTC23 expression was associated with coordinated pathway activation, malignant functional states, and distinct immune-associated features. Functionally, TTC23 depletion suppressed migratory capacity, increased apoptotic susceptibility, reduced short-term viability, and impaired long-term clonogenic survival, while sensitizing GBM cells to CPZ-associated anti-tumor phenotypes.
Conclusion:
Our multi-layer framework nominates TTC23 as a functionally relevant determinant associated with CPZ response in GBM and supports the CPZ-TTC23 axis as a candidate for biomarker-informed drug repurposing.
Insights
This study identifies TTC23 as a key target for repurposing chlorpromazine (CPZ) in glioblastoma (GBM). Targeting the CPZ-TTC23 axis may offer new therapeutic strategies for this lethal brain cancer.
Area of Science:
- Oncology
- Pharmacology
- Bioinformatics
Background:
- Glioblastoma (GBM) is a fatal brain tumor with high recurrence rates and limited treatment options.
- Drug repurposing is a viable strategy, but identifying specific targets for complex drugs like chlorpromazine (CPZ) is challenging.
Purpose of the Study:
- To identify actionable drug targets within GBM by integrating transcriptomic data with CPZ targets.
- To prioritize candidate genes for therapeutic intervention using network analysis and prognostic modeling.
- To investigate the role of TTC23 in GBM and its interaction with CPZ.
Main Methods:
- Integrated GBM transcriptomic data with known CPZ targets to identify intersecting genes.
- Constructed a protein-protein interaction network and developed a prognostic model to prioritize key genes.
- Utilized structure-informed docking and conformational sampling to assess TTC23-CPZ interaction.
- Analyzed TTC23 expression in relation to GBM pathways, oncogenic states, and immune contexture.
- Performed functional validation in GBM cell models to assess the impact of TTC23 modulation on GBM phenotypes and CPZ response.
Main Results:
- Network and prognostic analyses consistently identified TTC23 as a clinically relevant candidate gene.
- Structural analyses supported a plausible interaction between TTC23 and CPZ.
- Elevated TTC23 expression correlated with activated oncogenic pathways and distinct immune features in GBM.
- TTC23 depletion impaired GBM cell migration, viability, and survival, while enhancing sensitivity to CPZ.
Conclusions:
- The study nominates TTC23 as a crucial determinant of CPZ response in GBM.
- The CPZ-TTC23 axis represents a promising target for biomarker-informed drug repurposing in GBM treatment.
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