-associated gene signatures may help distinguish recurrent meningiomas and point to immune and drug-response hypotheses.
Evidence
An integrative bioinformatics analysis of GSE136661 and GSE173825 identified four CSA-signature genes, built an elastic net recurrence classifier with AUC 0.816, and linked recurrent tumors to immune infiltration patterns and candidate drugs.
Caveat
The findings come from dataset modeling and database screening, so the proposed markers, regulators, and drugs require biological and clinical validation.
Simplified
BACKGROUND: is intimately tied to tumorigenesis and progression, yet its exploration in meningiomas remains inadequate. In this study, we aim to unravel the role of cellular senescence-associated genes (CSA-genes) in meningioma recurrence and identify potential diagnostic markers and therapeutic targets.
METHODS: We analyzed GSE136661 and GSE173825 datasets to identify CSA-signature genes through differential expression analysis, weighted gene co-expression network analysis, protein-protein interaction network construction, and elastic net regression modeling. Functional enrichment, immune cell infiltration using CIBERSORT, and transcription factor prediction were performed. Potential drugs were screened using Enrichr database.
RESULTS: A total of 1827 differentially expressed genes (DEGs) were identified, among which 48 were cell senescence-associated differentially expressed genes (CSA-DEGs). Four key CSA-signature genes (CDK1, FOXM1, MYBL2, and BIRC5) were discovered by integrating elastic net regression and network algorithms. The elastic net model demonstrated strong classification performance with an area under the curve (AUC) of 0.816 in distinguishing recurrent meningiomas. Recurrent tumors exhibited significant immune heterogeneity, including increased neutrophils and M0 macrophages (p = 0.007), and CSA-genes were significantly correlated with immune infiltration and checkpoint molecules such as VSIR (p < 0.05). Transcription factor E2F1 was identified as a potential regulator of CSA-signature genes. Drug screening highlighted Dasatinib and Rapamycin as promising candidates with notable anti-meningioma potential.
CONCLUSION: Our findings highlight crucial genes and pathways in meningioma recurrence, introducing novel therapeutic candidates. These findings pave new avenues for further elucidating meningioma recurrence mechanisms and developing innovative treatments.
Key numbers
0.816
for classification performance
performance in classifying tumor types.
1827
identified
Total number of found in the analysis.
48
Cell senescence-associated identified
Number of identified from the total .
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