Abstract
PurposeGlioblastoma is one of the most aggressive nervous system neoplasms. Immunotherapy represents a hot spot and has not been included in standard treatments of glioblastoma. So in this study, we aim to filtrate an immune-related gene pairs (IRGPs) signature for predicting survival and immune heterogeneity.MethodsWe used gene expression profiles and clinical information of glioblastoma patients in the TCGA and CGGA datasets, dividing into discovery and validation cohorts. IRGPs significantly correlative with prognosis were selected to conduct an IRGPs signature. Low and high risk groups were separated by this IRGPs signature. Univariate and multivariate cox analysis were adopted to check whether risk can be a independent prognostic factor. Immune heterogeneity between different risk groups was analyzed via immune infiltration and gene set enrichment analysis (GSEA). Some different expressed genes between groups were selected to determine their relationship with immune cells and immune checkpoints.ResultsWe found an IRGPs signature consisting of 5 IRGPs. Different risk based on IRGPs signature is a independent prognostic factor both in the discovery and validation cohorts. High risk group has some immune positive cells and more immune repressive cells than low risk group by means of immune infiltration. We discovered some pathways are more active in the high risk group, leading to immune suppression, drug resistance and tumor evasion. In two specific signaling, some genes are over expressed in high risk group and positive related to immune repressive cells and immune checkpoints, which indicate aggression and immunotherapy resistance.ConclusionWe identified a robust IRGPs signature to predict prognosis and immune heterogeneity in glioblastoma patients. Some potential targets and pathways need to be further researched to make different patients benefit from personalized immunotherapy.
Highlights
Glioblastoma multiforme (GBM) is the most aggressive and malignant tumor in the central nervous system
The filtered data used immune-related genes (IRGs) downloaded from the ImmPort database to establish immune-related gene pairs (IRGPs). 56554 IRGPs were conducted from 724 immune-related genes
Screening IRGPs by means of the log-rank test, cox regression and multiple lasso regression, we selected 5 IRGPs and calculated immunerelated gene pairs index (IRGPI). These 5 IRGPs are composed of 9 unique IRGs, most of which relate to antigen processing and presentation, antimicrobials and cytokines (Table 1)
Summary
Glioblastoma multiforme (GBM) is the most aggressive and malignant tumor in the central nervous system. The current standard therapy involving tumor resection, radiotherapy and chemotherapy implemented in 2005 and have yet to be modified [1]. Despite this conventional treatments, the median survival time for GBM is despondingly 12-18 months [2]. The evolvement in genomics and proteomics has made researchers acquire prominent molecular biomarkers, while few lead to a robust and innovative signature on GBM therapy [3]. GBM immunotherapy is a research hot spot in recent years.
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