Systematic identification, development, and validation of prognostic biomarkers involving the tumor‐immune microenvironment for glioblastoma

Abstract

Gliomas are infiltrative neoplasms with a highly invasive nature. Due to its distinct genomic, genetic and epigenetic features, the immune prognostic signature (IPS) and immune microenvironment of glioblastoma (GBM) merit further research. We aimed to explore prognosis-related immune genes and develop an IPS model for predicting prognosis in GBM. RNA-sequencing data, as well as clinical information, from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) public cohorts were analyzed. To develop the IPS, least absolute shrinkage and selection operator (LASSO) Cox analysis was performed for immune-related genes that were differentially expressed between GBM and normal tissues. Then, interaction effects of the IPS on the immune microenvironment were systematically analyzed; the precise prognostic model was developed based on the IPS and clinical data and was then further validated. A total of 21 immune prognostic genes were identified based on GBM microenvironment status. An 8-gene IPS was established, and the GBM patients were effectively stratified into low-and high-risk groups in the TCGA cohort as a training set. Univariate and multivariate Cox analyses revealed that IPS was an independent prognostic factor, and the prognostic performance of individual IPS genes was systematically illustrated. In addition, a comprehensive and novel nomogram model was initially established to estimate overall survival in TCGA-GBM patients, and high-risk patients had higher levels of dendritic cell and neutrophil infiltration. Furthermore, the nomogram model was developed and validated in the CGGA validation set. The low-risk IPS was linked to a stronger response to anti-PD-L1 immunotherapy and clinical advantages in the IMvigor210 cohort. This novel IPS with promising biomarkers classifies GBM patients into subgroups with distinct clinical outcomes and immunophenotypes. Our findings and this resource may help to characterize the immune microenvironment, inform cancer immunotherapy and facilitate the development of precision immuno-oncology.

The Expression and Prognostic Values of Epidermal Growth Factor Receptor Family in Glioma

“…Blocking immune checkpoints has become a promising cancer treatment [66]. However, the relationship between the EGFR family and immune in ltration in gliomas has not been studied.…”

Research Supporting a Pilot Study of Metronomic Dapsone during Glioblastoma Chemoirradiation

“…The preponderance of evidence in human cancers points to a growth enhancing role in naturally occurring malignant disease—hence dapsone. Intratumoral neutrophils are a negative prognostic sign in GB and interestingly positively correlated with programmed death ligand-1 expression [ 64 , 65 ].…”

A New Epigenetic Model to Stratify Glioma Patients According to Their Immunosuppressive State

“…The clinical outcome of gliomas is strictly related with the composition and cell cross-talk of tumor microenvironment (TME), in particular with the immune texture in terms of the distinct immune cell types as well as the different immunosuppressive cell populations, such as T regulatory cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), dendritic cells and antigen-presenting cells specific to the brain such as microglia [ 5 , 6 , 7 ]. A significant infiltration of Tregs can be detected in a large fraction of gliomas, in particular in the GBM group.…”