A prognostic matrix gene expression signature defines functional glioblastoma phenotypes and niches
Interactions among tumor, immune, and vascular niches play major roles in glioblastoma (GBM) malignancy and treatment responses. The composition and heterogeneity of extracellular core matrix proteins (CMPs) that mediate such interactions are not well understood. Here, we present an analysis of the clinical relevance of CMP expression in GBM at bulk, single-cell, and spatial anatomical resolution. We show that CMP enrichment is associated with worse patient survival, specific driver oncogenic alterations, mesenchymal state, pro-tumor immune infiltration, and immune checkpoint expression. Matrisome expression is enriched in vascular and leading edge/infiltrative niches that are known to harbor glioma stem cells. Finally, we identify a 17-gene CMP signature, termed Matrisome 17 (M17), which is a stronger prognostic factor compared to MGMT promoter methylation status as well as canonical subtypes, and importantly, may predict responses to PD1 blockade. Patient stratification based on matrisome profiles can contribute to the selection and optimization of treatment strategies.
Authors
- Kisan Thapa (ORCID: https://orcid.org/0009-0007-2036-7351)
- Özgün Babur (ORCID: https://orcid.org/0000-0002-0239-5259)
- Nourhan Abdelfattah (ORCID: https://orcid.org/0000-0002-0556-0977)
- Anil Korkut (ORCID: https://orcid.org/0000-0001-8072-9026)
- Xubin Li (ORCID: https://orcid.org/0000-0003-1727-9215)
- Farach-Carson Mary
- Zeynep Dereli (ORCID: https://orcid.org/0000-0002-3486-5630)
- Meric Kinali (ORCID: https://orcid.org/0009-0000-2034-8336)
- Monika Vishnoi (ORCID: https://orcid.org/0009-0006-4924-1093)
- Behnaz Bozorgui (ORCID: https://orcid.org/0000-0003-0557-1681)
- Robert Rostomily (ORCID: https://orcid.org/0000-0003-1431-162X)
- Kyuson Yun
- Elisabeth K. Kong
- Zheng Yin
Institutions
- Houston Methodist (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of Washington (US)
- Cornell University (US)
- University of Massachusetts Boston (US)
- Weill Cornell Medicine (US)
- Rice University (US)
- The University of Texas Health Science Center at Houston (US)
Publication Details
- Journal
- Communications Biology
- Published
- 2026-01-05
- DOI
- https://doi.org/10.1038/s42003-025-09245-8
- Citations
- 1
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 36.93
Funders
- University of Texas at Austin
- National Institutes of Health
- University of Texas MD Anderson Cancer Center