{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:56:01Z","timestamp":1790762161372,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Glioblastoma (GBM) is characterized by marked intratumoral heterogeneity, diffuse invasion, and a profoundly immunosuppressive tumor microenvironment. In this study, we applied an integrative multi\u2010omics and radiogenomic framework to identify candidate biomarkers reflecting complementary dimensions of GBM heterogeneity. Public bulk transcriptomic datasets were integrated to define GBM\u2010related differentially expressed genes, which were intersected with curated microbiota\u2010associated gene sets as a hypothesis\u2010generating screening strategy. Machine\u2010learning models with SHAP interpretation were used for candidate\u2010gene prioritization, followed by survival\u2010association analysis, pan\u2010cancer comparison, Human Protein Atlas immunohistochemistry, CPTAC proteomics, immune infiltration analysis, single\u2010cell transcriptomics, spatial transcriptomics, in silico perturbation analysis, and MRI\u2010based radiogenomics. GBM samples showed enrichment of extracellular matrix organization, proliferative programs, immune\u2010related signaling, and vascular or endothelial pathways, with relative reductions in neural, synaptic, and myelin\u2010associated signatures. S100B and ITGB5 emerged as survival\u2010associated candidate markers with different biological contexts. Multi\u2010omics analyses suggested that S100B may reflect broadly distributed glial\u2010lineage and malignant\u2010state programs, whereas ITGB5 was more closely associated with focal extracellular matrix remodeling, stromal\u2010vascular interactions, and immunoregulatory niches. Radiogenomic analysis further suggested distinct MRI\u2010derived associations for the two genes, with the ITGB5\u2010related model retaining a broader radiomic signature and showing a more heterogeneous habitat pattern than the S100B\u2010related 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.<\/jats:p>","DOI":"10.1111\/cbdd.70396","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:39:56Z","timestamp":1789450796000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Multi\u2010Omics and Radiogenomic Analysis Identifies\n                    <scp>S100B<\/scp>\n                    and\n                    <scp>ITGB5<\/scp>\n                    as Complementary Candidate Biomarkers of Glioblastoma Heterogeneity"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1852-642X","authenticated-orcid":false,"given":"Xuhang","family":"Yang","sequence":"first","affiliation":[{"name":"Wenzhou Medical University  Wenzhou China"},{"name":"Department of Neurosurgery The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wenzhou Medical University  Wenzhou China"},{"name":"Department of Neurosurgery The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutuo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Wenzhou Medical University  Wenzhou China"},{"name":"Department of Neurosurgery The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Lin","sequence":"additional","affiliation":[{"name":"Wenzhou Medical University  Wenzhou China"},{"name":"Department of Neurosurgery The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"The Key Laboratory of Pediatric Hematology and Oncology Diseases of Wenzhou The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10143\u2010024\u201002823\u20100"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells15020135"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010020\u20106624\u2010y"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201093081\u20107"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876\u2010024\u201003447\u2010w"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14041092"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2018"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/neurosci6030075"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201017707\u2010w"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43856\u2010025\u201000767\u20100"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2023.2291679"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2024.106655"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2025.104657"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.03.029"},{"key":"e_1_2_13_16_1","doi-asserted-by":"crossref","unstructured":"Jackson C. 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