Integrated analysis of single-cell sequencing and weighted co-expression network identifies a novel signature based on cellular senescence-related genes to predict prognosis in glioblastoma.

Background: Glioblastoma (GBM) is a highly aggressive cancer with heavy mortality rates and poor prognosis. Cellular senescence exerts a pivotal influence on the development and progression of various cancers. However, the underlying effect of cellular senescence on the outcomes of patients with GBM remains to be elucidated.

Methods: Transcriptome RNA sequencing data with clinical information and single-cell sequencing data of GBM cases were obtained from CGGA, TCGA, and GEO (GSE84465) databases respectively. Single-sample gene set enrichment analysis (ssGSEA) analysis was utilized to calculate the cellular senescence score. WGCNA analysis was employed to ascertain the key gene modules and identify differentially expressed genes (DEGs) associated with the cellular senescence score in GBM. The prognostic senescence-related risk model was developed by least absolute shrinkage and selection operator (LASSO) regression analyses. The immune infiltration level was calculated by microenvironment cell populations counter (MCPcounter), ssGSEA, and xCell algorithms. Potential anti-cancer small molecular compounds of GBM were estimated by "oncoPredict" R package.

Results: A total of 150 DEGs were selected from the pink module through WGCNA analysis. The risk-scoring model was constructed based on 5 cell senescence-associated genes (CCDC151, DRC1, C2orf73, CCDC13, and WDR63). Patients in low-risk group had a better prognostic value compared to those in high-risk group. The nomogram exhibited excellent predictive performance in assessing the survival outcomes of patients with GBM. Top 30 potential anti-cancer small molecular compounds with higher drug sensitivity scores were predicted.

Conclusion: Cellular senescence-related genes and clusters in GBM have the potential to provide valuable insights in prognosis and guide clinical decisions.