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

Overview

1. Graduate School, Dalian Medical University, Dalian 116044, China
2. Department of Neurosurgery, Dalian Municipal Central Hospital, Dalian 116033, China; (Z.J.)
3. Faculty of Medicine, Dalian University of Technology, Dalian 116024, China

Abstract

Background/Objectives: TGFB2 is the dominant TGF-β isoform in glioma, and isolated experimental studies have implicated it in immunosuppressive signaling; however, its prognostic value and systematic association with the tumor immune microenvironment across the diffuse glioma spectrum have not been comprehensively characterized in large clinical cohorts. Methods: A multi-cohort transcriptomic study was conducted using TCGA (n = 667) as discovery and CGGA (n = 404) as validation, integrating survival analysis, functional enrichment, immune deconvolution by ssGSEA and MCP-counter, immune checkpoint correlation, and TISCH2-based single-cell localization. Results: TGFB2 was consistently overexpressed in glioma relative to normal brain at both mRNA and protein levels, with expression highest in GBM (median 10.60 vs. 8.45 in LGG; p < 2.2 × 10−16) and increasing across WHO grade. High TGFB2 predicted worse overall survival in both cohorts (TCGA: 648 vs. 2907 days; CGGA: 863 vs. 3107 days; both p < 0.0001), with 3-year AUCs of 0.823 and 0.714, and retained independent prognostic significance in the CGGA multivariate model (HR = 1.343; p = 3.2 × 10−4). Hallmark GSEA identified consistent enrichment of interferon signaling, epithelial–mesenchymal transition, TNFα/NF-κB, and IL-6/JAK/STAT3 pathways. ssGSEA and MCP-counter concordantly demonstrated significantly expanded myeloid, monocytic, and stromal populations across both cohorts. TGFB2 correlated positively with PD-L1, TIM-3, ICOS (ρ = 0.449), IL2RA (ρ = 0.397), CTLA4 (ρ = 0.375), and TIGIT (ρ = 0.170) in TCGA, with all associations replicated in CGGA. Conclusions: TGFB2 is an adverse prognostic biomarker in diffuse glioma coupled to a myeloid-enriched, multi-checkpoint-activated tumor microenvironment, supporting its evaluation as a stratification biomarker in TGF-β/checkpoint combination immunotherapy trials.

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

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.

Data

Datasets cited

• geo:GSE148842 — at NCBI GEO; found in the text, “2.8. Single-Cell Localization”

Data Availability Statement

The raw data supporting the findings of this study are publicly available from the following repositories: TCGA RNA-seq expression and clinical data were downloaded from the Genomic Data Commons (GDC) portal (https://gdc.cancer.gov/). Molecular annotation for TCGA samples was obtained from cBioPortal PanCancer Atlas (https://www.cbioportal.org/). CGGA RNA-seq (mRNAseq_693) expression and clinical data were downloaded from the CGGA portal (https://www.cgga.org.cn/). Single-cell RNA-seq data were accessed through TISCH2 (https://tisch.compbio.cn/). Protein-level expression data were accessed through UALCAN (https://ualcan.path.uab.edu). Processed results supporting all figures and conclusions are provided as Supplementary Tables S1–S5 and Supplementary Figures S1–S6. Additional data tables and all R analysis scripts 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, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 6 keywords, 1 funder, 75 references.

Cite

This paper

Balawi, E., Jiang, Z., Wang, X., & Chen, D. (2026). TGFB2 as a Prognostic Biomarker Associated with Myeloid-Enriched, Multi-Checkpoint-Activated Immunosuppression in Diffuse Glioma: A Multi-Cohort Transcriptomic Study. Cancers, 18(13), 2092. https://doi.org/10.3390/cancers18132092

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/s41586-026-10612-6 [code]

Acquired genetic and cell-state changes in IDH-mutant glioma progression.

Journal: Nature

In common: other condition, 7 references

[2] doi:10.3390/ijms27136068 [code]

Loss of Neuropeptide Y Signaling Accompanies the Neural-to-Mesenchymal Transcriptional Transition in Glioblastoma: A Multi-Scale Transcriptomic Analysis.

Journal: International journal of molecular sciences

In common: genetics / omics, other condition, 7 references

[3] doi:10.32604/or.2026.079221

Single-Cell Sequencing Reveals the Heterogeneity of Glioma and Identifies IGFBP2 as A Potential Therapeutic Target.

Journal: Oncology research

In common: genetics / omics, other condition, 6 references

[4] doi:10.1080/17501911.2026.2691031

Promoter methylation-associated brain-enriched long noncoding RNAs in glioblastoma: a multi-cohort public epigenomic re-analysis.

Journal: Epigenomics

In common: genetics / omics, other condition, 6 references

[5] doi:10.1016/j.omton.2026.201215

Reprogramming the immune suppressive tumor microenvironment in glioma enhances the efficacy of immune-mediated gene therapy.

Journal: Molecular therapy. Oncology

In common: other condition, 5 references

[6] doi:10.1186/s40478-026-02318-7

Glioblastoma cells utilize evolutionarily adapted cell metabolism to promote their malignant proliferation.

Journal: Acta neuropathologica communications

In common: other condition, 6 references

[7] doi:10.3389/fonc.2026.1742452

SLC10A3 drives glioblastoma progression by remodeling the immunosuppressive microenvironment and promoting M2 macrophage migration.

Journal: Frontiers in oncology

In common: genetics / omics, other condition, 5 references

[8] doi:10.1186/s12967-026-08266-z [code]

Single-cell multi-omic integration analysis prioritizes druggable genes and reveals cell-type-specific causal effects in glioblastomagenesis.

Journal: Journal of translational medicine

In common: genetics / omics, other condition, 5 references

[9] doi:10.1016/j.xcrm.2026.102766 [code]

A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma.

Journal: Cell reports. Medicine

In common: genetics / omics, other condition, 5 references

[10] doi:10.3390/cancers18162616

Decitabine Reprograms Temozolomide-Resistant Glioblastoma Through Epigenetic Reactivation and Mesenchymal Attenuation: A Multi-Omics Study.

Journal: Cancers

In common: genetics / omics, other condition, 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.