Network-driven prioritization and functional phenotyping nominate TTC23 as a biomarker-informed target in chlorpromazine repurposing for glioblastoma.

Overview

1. Department of Neurosurgery, Ziyang Central Hospital, West China Hospital of Sichuan University-Ziyang Hospital, Ziyang, China
2. Outpatient Department, Ziyang Central Hospital, West China Hospital of Sichuan University-Ziyang Hospital, Ziyang, China

Abstract

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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

• geo:GSE4290, at NCBI GEO; found in “Data availability statement”

Data availability statement

The datasets analyzed in this study are publicly available. Bulk transcriptomic data were obtained from the Gene Expression Omnibus (GEO) under accession number GSE4290 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4290) and from The Cancer Genome Atlas (TCGA-GBM) project. Single-cell RNA-seq data used for cell-cycle–resolved analysis were obtained from GEO under accession number GSE146773 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146773). All other data generated during this study are included in the article and its supplementary material or are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 6 authors, 7 keywords, 65 references, 3 RRIDs.

Cite

This paper

Hao, J., Liu, H., Ye, Y., Lv, J., Xue, F., & Cai, Y. (2026). Network-driven prioritization and functional phenotyping nominate TTC23 as a biomarker-informed target in chlorpromazine repurposing for glioblastoma. Frontiers in pharmacology, 17, 1797067. https://doi.org/10.3389/fphar.2026.1797067

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1038/s41598-026-43219-y

Identification of NFE2L2 as a key biomarker associated with pyroptosis in gliomas through bioinformatics and experiments.

Journal: Scientific reports

In common: other condition, 7 references

[2] doi:10.1016/j.isci.2026.115361

Glioblastoma invasion into different organoid hosts reveals cell-intrinsic and proliferative migratory programs.

Journal: iScience

In common: other condition, 5 references

[3] doi:10.1111/jcmm.71154

Mitophagy-Oxidative Stress Molecular Subtypes Define an Immunosuppressive Ecosystem and Vulnerabilities in Glioblastoma.

Journal: Journal of cellular and molecular medicine

In common: other condition, 6 references

[4] doi:10.1007/s12672-026-04980-8

PARP4 drives tumor progression by promoting glioma cell proliferation and invasion as a potential therapeutic target.

Journal: Discover oncology

In common: NCBI GEO GSE4290, clinical / translational, other condition

[5] doi:10.3390/cancers18132092

TGFB2 as a Prognostic Biomarker Associated with Myeloid-Enriched, Multi-Checkpoint-Activated Immunosuppression in Diffuse Glioma: A Multi-Cohort Transcriptomic Study.

Journal: Cancers

In common: other condition, 5 references

[6] doi:10.2147/ijgm.s605071

Mendelian Randomization and Single-Cell RNA Sequencing Reveal CKAP4 and PFDN5 as Tumor Cell-Specific Causal Genes for Glioblastoma.

Journal: International journal of general medicine

In common: other condition, 5 references

[7] doi:10.1002/alz.71804

A meta-refined human Alzheimer's disease-associated gene subset shows partial mouse-model pathway correspondence and limited cross-cohort machine-learning transportability.

Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association

In common: 5 references

[8] doi:10.1111/bpa.70125

From patient to tumor organoid: Culture protocol choice controls glioblastoma tumor architecture and identity.

Journal: Brain pathology (Zurich, Switzerland)

In common: clinical / translational, other condition, 4 references

[9] doi:10.1038/s41467-026-76587-0 [code]

Uncovering the signaling networks of disseminated glioblastoma cells in vivo with INSIGHT.

Journal: Nature communications

In common: other condition, 5 references

[10] doi:10.1007/s12031-026-02598-7

A Lipoylation-PDH-TCA Transcriptional Deficit in the Alzheimer's Disease Cortex - Donor-level Multi-cohort Evidence with Neuronal-composition, Disease-specificity and Matched-null Controls.

Journal: Journal of molecular neuroscience : MN

In common: 5 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.