Abstract
Glioma is one of the most fatal tumors in central nervous system. Previous studies gradually revealed the association between tumor microenvironment and the prognosis of gliomas patients. However, the correlation between tumor-infiltrating immune cell and stromal signatures are unknown. In our study, we obtained gliomas samples from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). The landscape of tumor infiltrating immune cell subtypes in gliomas was calculated by CIBERSORT. As a result, we found high infiltration of macrophages was correlated with poor outcome (P < 0.05). Then functional enrichment analysis of high/low macrophage-infiltrating groups was performed by GSEA. The results showed three gene sets includes 102 core genes about angiogenesis were detected in high macrophage-infiltrating group. Next, we constructed PPI network and analyzed prognostic value of 102 core genes. We found that five stromal signatures indicated poor prognosis which including HSPG2, FOXF1, KDR, COL3A1, SRPX2 (P < 0.05). Five stromal signatures were adopted to construct a classifier. The classifier showed powerful predictive ability (AUC = 0.748). Patients with a high risk score showed poor survival. Finally, we validated this classifier in TCGA and the result was consistent with CGGA. Our investigation of tumor microenvironment in gliomas may stimulate the new strategy in immunotherapy. Five stromal signature correlated with poor prognosis also provide a strong predator of gliomas patient outcome.
Highlights
Glioma is the most deadly central nervous system (CNS) tumor
Based on Chinese Glioma Genome Atlas (CGGA) RNA-seq datasets, the landscape of 22 tumor-infiltrating immune cells in gliomas was analyzed by CIBERSORT
Three gene sets includes 102 core genes about angiogenesis were detected in high macrophage-infiltrating group
Summary
Glioma is the most deadly central nervous system (CNS) tumor. Patients with gliomas always show poor outcome, and their median overall survival remains from 14.6 to 16.8 months. High expression of stromal signatures correlated with macrophage infiltration, angiogenesis and poor prognosis in glioma microenvironment. Previous study integrated several tumor microenvironment related genes based on The Cancer Genome Atlas (TCGA) database applied by ESTIMATE algorithmbased immune scores (Chen et al, 2018). The correlation between tumor-infiltrating immune cells and stromal signatures in gliomas are still unknown. The Chinese Glioma Genome Atlas (CGGA) is a database which contains 2,000 glioma samples from Chinese cohorts This database was finished a large scale update in July 2019, and 693 mRNA sequencings and matched clinical data were provided, which includes: histology, WHO grades, age, gender, chemotherapy, radiotherapy, overall survival. Patients with a high risk score (RS) showed poor survival We validated this classifier in the TCGA database and the result was consistent with the CGGA database. The results provide a comprehensive view of the tumor microenvironment and may stimulate new strategies of immunotherapy in Chinese glioma patients
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