Comprehensive Analysis Uncovers Prognostic and Immunogenic Characteristics of Cellular Senescence for Gliomas

Abstract

Abstract Background Cellular senescence is considered to be an important correlate of tumorigenesis and progression, but the correlation between cellular senescence and immune infiltration of tumors remains unclear in glioma. The prognostic value of cellular senescence in gliomas with immune infiltration needs further investigation. Methods We obtained data from TCGA for GBM patients and LGG patients, followed by screening these genes by LASSO-COX based on genes associated with cellular senescence obtained from CellAge thereby obtaining survival-related signature genes, followed by KM analysis, ROC analysis, PCA analysis and immunostaining profiles to verify the risk score as a prognostic indicator of independence and plotting bar lines, and exploring the biological pathways associated with the high-risk group by GSEA analysis. The signature was also validated by combining the genetic information obtained from the China Glioma Genome Atlas (CGGA) database for GBM patients and LGG patients. Results We constructed a prognostic signature for five cellular senescence-related genes. They were CENPA, IGFBP-5, TNFSF13, PATZ1 & CDK6. The independence of the risk score as a prognostic indicator was validated by KM analysis, ROC analysis, PCA analysis, and immunohistochemical results. The prognosis of glioma patients was established from a plotted nomogram. We then found that the high-risk group was significantly enriched for pathways in the cell cycle, nuclear division regulation, CD40 signalling pathway and p53 signalling pathway by GSEA analysis. ssGSEA results indicated that the high-risk group was associated with tumor-infiltrating immune cells, including MDSCs, macrophages and Tregs. Conclusions We analyzed the clinical significance of different risk groups on glioma prognosis and the role in the immune landscape by constructing an independent prognostic signature based on cellular senescence correlation, which may help to develop personalized immunotherapy strategies for oncologists.