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Integrated Multi-Omics and Radiogenomic Analysis Identifies S100B and ITGB5 as Complementary Candidate Biomarkers of Glioblastoma Heterogeneity.

Overview

Authors: Xuhang Yang1,2, Yusong Zhang1,2, Yutuo Zheng1,2, Jian Lin1,2,3
ORCID iDs: Xuhang Yang
  1. Wenzhou Medical University, Wenzhou, China
  2. Department of Neurosurgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  3. The Key Laboratory of Pediatric Hematology and Oncology Diseases of Wenzhou, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Journal: Chemical biology & drug design, volume 108, issue 3, article e70396
Dates: received 28 June 2026; accepted 28 August 2026; published online 14 September 2026; in print September 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1111/cbdd.70396 · PMID 42740387 · PMCID PMC13575307 · OpenAlex W7213316086
Open access: hybrid, a free copy (OpenAlex)
Status: code on request
Categories: genetics / omics (modality), structural MRI / diffusion (modality), human (organism), other condition (population)
Methods: Connectivity, Statistics, Smoothing, state filtering, decompositions, Machine learning, fMRI & imaging
Keywords: glioblastoma, heterogeneity, ITGB5, microbiota‐associated genes, multi‐omics, radiogenomics, S100B, single‐cell transcriptomics, spatial transcriptomics, tumor microenvironment
MeSH: Biomarkers, Tumor*, Brain Neoplasms*, Glioblastoma*, S100 Calcium Binding Protein beta Subunit*, Humans, Machine Learning, Magnetic Resonance Imaging, Multiomics, Radiomics, Spatial Transcriptomics, Tumor Microenvironment (* major topic)
Topic: Ferroptosis and cancer prognosis (Pulmonary and Respiratory Medicine, Medicine), according to OpenAlex
Citations: not cited yet (Europe PMC); 40 references in the paper

Abstract

Glioblastoma (GBM) is characterized by marked intratumoral heterogeneity, diffuse invasion, and a profoundly immunosuppressive tumor microenvironment. In this study, we applied an integrative multi‐omics and radiogenomic framework to identify candidate biomarkers reflecting complementary dimensions of GBM heterogeneity. Public bulk transcriptomic datasets were integrated to define GBM‐related differentially expressed genes, which were intersected with curated microbiota‐associated gene sets as a hypothesis‐generating screening strategy. Machine‐learning models with SHAP interpretation were used for candidate‐gene prioritization, followed by survival‐association analysis, pan‐cancer comparison, Human Protein Atlas immunohistochemistry, CPTAC proteomics, immune infiltration analysis, single‐cell transcriptomics, spatial transcriptomics, in silico perturbation analysis, and MRI‐based radiogenomics. GBM samples showed enrichment of extracellular matrix organization, proliferative programs, immune‐related signaling, and vascular or endothelial pathways, with relative reductions in neural, synaptic, and myelin‐associated signatures. S100B and ITGB5 emerged as survival‐associated candidate markers with different biological contexts. Multi‐omics analyses suggested that S100B may reflect broadly distributed glial‐lineage and malignant‐state programs, whereas ITGB5 was more closely associated with focal extracellular matrix remodeling, stromal‐vascular interactions, and immunoregulatory niches. Radiogenomic analysis further suggested distinct MRI‐derived associations for the two genes, with the ITGB5‐related model retaining a broader radiomic signature and showing a more heterogeneous habitat pattern than the S100B‐related model. These exploratory findings support S100B and ITGB5 as complementary candidate biomarkers of GBM heterogeneity and provide a basis for future experimental, multicenter, and prospective validation.

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

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Data

Datasets cited

Data Availability Statement

The transcriptomic and single‐cell RNA sequencing datasets analyzed during the current study are available in public repositories, including TCGA, CGGA, GTEx, and the Gene Expression Omnibus (GEO) database under the accession numbers GSE116520 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE116520), GSE263588 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE263588), GSE83300 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83300), GSE119834 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119834), GSE137900 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137900), GSE135045 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE135045), and GSE237183 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE237183). All custom scripts, computational pipelines, and processed analytical data underlying the results reported in this manuscript are available from the corresponding authors 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 3, 28 September 2026

  • Publisher: — → Wiley

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 10 keywords, 11 MeSH terms, 40 references.

Cite

This paper

Yang, X., Zhang, Y., Zheng, Y., & Lin, J. (2026). Integrated Multi-Omics and Radiogenomic Analysis Identifies S100B and ITGB5 as Complementary Candidate Biomarkers of Glioblastoma Heterogeneity. Chemical biology & drug design, 108(3), e70396. https://doi.org/10.1111/cbdd.70396

BibTeX

@article{yang2026integrated,
author = {Yang, Xuhang and Zhang, Yusong and Zheng, Yutuo and Lin, Jian},
title = {{Integrated Multi-Omics and Radiogenomic Analysis Identifies S100B and ITGB5 as Complementary Candidate Biomarkers of Glioblastoma Heterogeneity}},
journal = {Chemical biology \& drug design},
year = {2026},
month = sep,
volume = {108},
number = {3},
pages = {e70396},
publisher = {Wiley},
issn = {1747-0277},
doi = {10.1111/cbdd.70396},
url = {https://doi.org/10.1111/cbdd.70396},
pmid = {42740387},
pmcid = {PMC13575307}
}

RIS

TY - JOUR
AU - Yang, Xuhang
AU - Zhang, Yusong
AU - Zheng, Yutuo
AU - Lin, Jian
TI - Integrated Multi-Omics and Radiogenomic Analysis Identifies S100B and ITGB5 as Complementary Candidate Biomarkers of Glioblastoma Heterogeneity
T2 - Chemical biology & drug design
J2 - Chem Biol Drug Des
PY - 2026
DA - 2026/09/01
VL - 108
IS - 3
SP - e70396
SN - 1747-0277
PB - Wiley
DO - 10.1111/cbdd.70396
UR - https://doi.org/10.1111/cbdd.70396
LA - en
ER -

CSL-JSON

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