Abstract
Background: as the most common malignancy of the central nervous system, low-grade glioma (LGG) patients suffered a poor prognosis. Tumor microenvironment, especially immune components, plays an important role in the progression of tumors. Thus, it is critical to explore the key immune-related genes, a comprehensive understanding of the TME in LGG helps us find novel cancer biomarkers and therapeutic targets. Methods: the GPSM3 expression level and the correlations between clinical characteristics and GPSM3 levels were analyzed with the data from CGGA and TCGA dataset. Univariate and multivariate cox regression model were built to predict the prognosis of LGG patients with multiple factors. Then the correlation between GPSM3 with immune cell infiltration was explored by ESTIMATE, CIBERSORT and TIMER2.0. At last, the correlation analyzed between GPSM3 expression and immune checkpoint related genes were also analyzed. Results: GPSM3 expression was overexpressed in LGG and negatively correlated to the GPSM3 DNA methylation. Univariate and multivariate Cox analysis demonstrated that GPSM3 expression was an independent prognostic factor in LGG patients. Functional characterization of GPSM3 revealed that it was associated with many immune processes to tumor cells. GPSM3 expression was positive related to the immune score, Stromal scores and ESTIMATE scores, but negative related to the Tumor purity. Immune features in the TME of GPSM3-high LGG group is characterized by a higher infiltrating of regulatory T cells, neutrophils, macrophages M2, and a lower proportion of monocytes than to the GPSM3-low group. Furthermore, GPSM3 expression exhibited significant correlations with the immune checkpoint-related genes, especially PD-1, PD-L1, PD-L2, CTLA4 and TIM3. Conclusions: these findings proved that GPSM3 could serve as a prognostic biomarker and potential immunotherapy target for LGG.
Highlights
Glioma is the most common primary tumor of the central nervous system (CNS), accounting for slightly more than 50% of intracranial malignancies [1]
We investigated the association between GPSM3 expression in low-grade glioma (LGG) and the abundance of immune cell infiltration, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells via TIMER2.0
The results showed a higher GPM3 mRNA expression in elderly patients than in young patients, but no significant difference in GPSM3 mRNA levels was indicated by sex and World Health Organization (WHO) grade (Figure 1E–G)
Summary
Glioma is the most common primary tumor of the central nervous system (CNS), accounting for slightly more than 50% of intracranial malignancies [1]. According to the World Health Organization (WHO) classification of tumors in the CNS, gliomas are classified into low-grade (LGG, WHO grades I–II) and high-grade (HGG, WHO grades III–IV) [2]. Immune cells and stromal cells are the main non-tumor components of TME [3]. By targeting the immune checkpoint in TME, anti-cytotoxic Tlymphocyte associated protein 4 (CTLA4), anti-programmed cell death 1 (PD-1), and anti-CD274/PD-L1havebeen shown to be the most effective immunotherapy methods for cancer [7,8]. It is crucial to identify the more effective genes related to TME and the potential mechanisms of interaction between TME and glioma cells, which will help to improve the efficacy of immunotherapies for LGG
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