High expression of stromal signatures correlated with macrophage infiltration, angiogenesis and poor prognosis in glioma microenvironment

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.

Expression of m6A Regulators Correlated With Immune Microenvironment Predicts Therapeutic Efficacy and Prognosis in Gliomas

“…Besides, the immune and stroma scores and immune cell infiltration was higher in cluster1. However, previous studies revealed that high immune and stroma scores as well as high infiltration of macrophages were associated with poor prognosis, which was reversed with our results in consensus clustering (Deng et al, 2020;Ni et al, 2020;Tian et al, 2020). Therefore, we further constructed a risk model to explore and validate the association between m6A regulators and the immune microenvironment.…”

A Prognostic Microenvironment-Related Immune Signature via ESTIMATE (PROMISE Model) Predicts Overall Survival of Patients With Glioma

“…Although numerous studies have examined gene signatures related to TME in patients with glioma, their efforts could not be translated to clinical practice due to vague cutoff values across different data sets (15)(16)(17), lack of comparisons with established classification (15,16), inferior classification accuracy compared to tumor grade (17), and a relatively large number of genes (16). In contrast, our PROMISE model with four genes embedded used an identical cutoff value across different data sets (LGG and GBM in both TCGA and CGGA) and presented distinct survival rates between risk groups.…”

“…Further, the number of genes stymies practical clinical implementation. Tian Y et al (17) developed a stromal classifier based on local macrophage infiltration via Cibersort, but it was not validated in LGG and GBM independently. Plus, the predictive performance of the classifier was inferior to tumor grade, indicating the proposed classifier was not clinically-relevant.…”

Construction of a Prognostic Gene Signature Associated with Immune Infiltration in Glioma: A Comprehensive Analysis Based on the CGGA

“…Tumor immune infiltration involves multiple immune cells whose functions are significantly altered in glioma. The research of Tian et al notes that M0 and M2 tumor-associated macrophages (TAMs) play a protumor role, while M1 TAMs play an antitumor role [ 4 ]. The glioblastoma microenvironment has been demonstrated to increase counts of myeloid-derived suppressor cells, which block T cell and natural-killer (NK) cell functions, resulting in an immunocompromised microenvironment [ 5 ].…”