TY - JOUR
T1 - A prognostic matrix code defines functional glioblastoma phenotypes and niches
AU - Vishnoi, Monika
AU - Dereli, Zeynep
AU - Yin, Zheng
AU - Kong, Elisabeth K
AU - Kinali, Meric
AU - Thapa, Kisan
AU - Babur, Ozgun
AU - Yun, Kyuson
AU - Abdelfattah, Nourhan
AU - Li, Xubin
AU - Bozorgui, Behnaz
AU - Rostomily, Robert C
AU - Korkut, Anil
PY - 2023/6/8
Y1 - 2023/6/8
N2 - Interactions among tumor, immune and vascular niches play major roles in driving glioblastoma (GBM) malignancy and treatment responses. The composition, heterogeneity, and localization of extracellular core matrix proteins (CMPs) that mediate such interactions, however, are not well understood. Here, we characterize functional and clinical relevance of genes encoding CMPs in GBM at bulk, single cell, and spatial anatomical resolution. We identify a "matrix code" for genes encoding CMPs whose expression levels categorize GBM tumors into matrisome-high and matrisome-low groups that correlate with worse and better survival, respectively, of patients. The matrisome enrichment is associated with specific driver oncogenic alterations, mesenchymal state, infiltration of pro-tumor immune cells and immune checkpoint gene expression. Anatomical and single cell transcriptome analyses indicate that matrisome gene expression is enriched in vascular and leading edge/infiltrative anatomic structures that are known to harbor glioma stem cells driving GBM progression. Finally, we identified a 17-gene matrisome signature that retains and further refines the prognostic value of genes encoding CMPs and, importantly, potentially predicts responses to PD1 blockade in clinical trials for GBM. The matrisome gene expression profiles may provide biomarkers of functionally relevant GBM niches that contribute to mesenchymal-immune cross talk and patient stratification to optimize treatment responses.
AB - Interactions among tumor, immune and vascular niches play major roles in driving glioblastoma (GBM) malignancy and treatment responses. The composition, heterogeneity, and localization of extracellular core matrix proteins (CMPs) that mediate such interactions, however, are not well understood. Here, we characterize functional and clinical relevance of genes encoding CMPs in GBM at bulk, single cell, and spatial anatomical resolution. We identify a "matrix code" for genes encoding CMPs whose expression levels categorize GBM tumors into matrisome-high and matrisome-low groups that correlate with worse and better survival, respectively, of patients. The matrisome enrichment is associated with specific driver oncogenic alterations, mesenchymal state, infiltration of pro-tumor immune cells and immune checkpoint gene expression. Anatomical and single cell transcriptome analyses indicate that matrisome gene expression is enriched in vascular and leading edge/infiltrative anatomic structures that are known to harbor glioma stem cells driving GBM progression. Finally, we identified a 17-gene matrisome signature that retains and further refines the prognostic value of genes encoding CMPs and, importantly, potentially predicts responses to PD1 blockade in clinical trials for GBM. The matrisome gene expression profiles may provide biomarkers of functionally relevant GBM niches that contribute to mesenchymal-immune cross talk and patient stratification to optimize treatment responses.
U2 - 10.1101/2023.06.06.543903
DO - 10.1101/2023.06.06.543903
M3 - Article
C2 - 37333072
JO - bioRxiv
JF - bioRxiv
ER -