Increased Microglia/Macrophage Gene Expression in a Subset of Adult and Pediatric Astrocytomas

摘要: Glioblastoma (GBM) is a highly malignant brain tumor with dismal prognosis. Gene expression profiling of GBM has revealed clinically relevant subtypes, and this provides exciting opportunities to better understand disease pathogenesis. Results from an increasing number studies demonstrate role for the immune response in cancer progression, yet it unclear how differs across subtypes affects outcome. Utilizing gene data The Cancer Genome Atlas Project Expression Omnibus database, we enrichment response-related mesenchymal subtype adult (n = 173) pediatric high-grade gliomas 53). In independent cohort astrocytomas 24) UCSF, stratified tumors into confirmed these findings. Using novel cell-specific signatures selective microglia/macrophage-related genes subtype. Furthermore, immunostaining showed significantly higher cell numbers microglia/macrophages versus non-mesenchymal (p 0.04). Interestingly, shortest survival had significant but was not true GBMs. Consistent association poor outcome, were represented prognosis signature, related macrophage recruitment activation being most strongly associated (p<0.05) using CoxBoost multivariate modeling. microglia/macrophage high signature derived quantification tumor-infiltrating cells GBM, identified characteristic CD4 T cells, granulocytes, 573). These support response, particularly biology important subset GBM. Identification may be future therapeutic stratification.