Comprehensive Analysis of Inflammatory Response–Related Genes, and Prognosis and Immune Infiltration in Patients With Low-Grade Glioma

Abstract

Background: Although low-grade glioma (LGG) has a good prognosis, it is prone to malignant transformation into high-grade glioma. It has been confirmed that the characteristics of inflammatory factors and immune microenvironment are closely related to the occurrence and development of tumors. It is necessary to clarify the role of inflammatory genes and immune infiltration in LGG.Methods: We downloaded the transcriptome gene expression data and corresponding clinical data of LGG patients from the TCGA and GTEX databases to screen prognosis-related differentially expressed inflammatory genes with the difference analysis and single-factor Cox regression analysis. The prognostic risk model was constructed by LASSO Cox regression analysis, which enables us to compare the overall survival rate of high- and low-risk groups in the model by Kaplan–Meier analysis and subsequently draw the risk curve and survival status diagram. We analyzed the accuracy of the prediction model via ROC curves and performed GSEA enrichment analysis. The ssGSEA algorithm was used to calculate the score of immune cell infiltration and the activity of immune-related pathways. The CellMiner database was used to study drug sensitivity.Results: In this study, 3 genes (CALCRL, MMP14, and SELL) were selected from 9 prognosis-related differential inflammation genes through LASSO Cox regression analysis to construct a prognostic risk model. Further analysis showed that the risk score was negatively correlated with the prognosis, and the ROC curve showed that the accuracy of the model was better. The age, grade, and risk score can be used as independent prognostic factors (p < 0.001). GSEA analysis confirmed that 6 immune-related pathways were enriched in the high-risk group. We found that the degree of infiltration of 12 immune cell subpopulations and the scores of 13 immune functions and pathways in the high-risk group were significantly increased by applying the ssGSEA method (p < 0.05). Finally, we explored the relationship between the genes in the model and the susceptibility of drugs.Conclusion: This study analyzed the correlation between the inflammation-related risk model and the immune microenvironment. It is expected to provide a reference for the screening of LGG prognostic markers and the evaluation of immune response.

Identification of Gender- and Subtype-Specific Gene Expression Associated with Patient Survival in Low-Grade and Anaplastic Glioma in Connection with Steroid Signaling

“…These findings support the role of immunity in the prognosis of anaplastic glioma. Indeed, an immune-response signature was found in the IDHwt high-risk group and was correlated with a poor prognosis for LGG patients [ 35 ]. Recently, Song et al identified a 120-gene immune infiltration signature differentially expressed in low-grade glioma, compared with the normal brain, and selected a 20-gene immune infiltration signature that could predict the survival of the patients.…”

Research progress of anti-glioma chemotherapeutic drugs (Review)

“…Low-grade gliomas will typically relapse after initial treatment. Following recurrence, low-grade gliomas can transform into high-grade gliomas ( 6 – 8 ). The incidence of glioma accounts for ~40% of all malignancies in the central nervous system tumors, which is highly invasive and infiltrative ( 9 ).…”

GPCR genes as a predictor of glioma severity and clinical outcome

“…For example, genes related to inflammation, energy metabolism, autophagy and DNA methylation have previously been reported as prognostic markers of glioma. 10 – 14 Furthermore, various genetic alterations, such as mutations in the IDH1 , IDH2 and P53 genes, altered expression of epidermal growth factor receptor and aberrant MGMT promoter methylation status, have been reported in gliomas. 15 – 19…”

“…For example, genes related to inflammation, energy metabolism, autophagy and DNA methylation have previously been reported as prognostic markers of glioma. [10][11][12][13][14] Furthermore, various genetic alterations, such as mutations in the IDH1, IDH2 and P53 genes, altered expression of epidermal growth factor receptor and aberrant MGMT promoter methylation status, have been reported in gliomas. [15][16][17][18][19] G-protein-coupled receptors (GPCRs), a family of membrane receptors, play an important role in cellular signalling involving ligands, hormones, neurotransmitters and proteases.…”