Identifying Predictive Gene Expression and Signature Related to Temozolomide Sensitivity of Glioblastomas

Frontiers in Oncology
Hong-Qing CaiJing-Hai Wan

Abstract

Temozolomide (TMZ) is considered a standard chemotherapeutic agent for glioblastoma (GBM). Characterizing the biological molecules and signaling pathways involved in TMZ sensitivity would be helpful for selecting therapeutic schemes and evaluating prognosis for GBM. Thus, in the present study, we selected 34 glioma cell lines paired with specific IC50 values of TMZ obtained from CancerRxGene and RNA-seq data downloaded from the Cancer Cell Line Encyclopedia to identify genes related to TMZ sensitivity. The results showed that 1,373 genes were related to the response of GBM cells to TMZ. Biological function analysis indicated that epithelial-mesenchymal transition, Wnt signaling, and immune response were the most significantly activated functions in TMZ-resistant cell lines. Additionally, negative regulation of telomere maintenance via telomerase was enriched in TMZ-sensitive glioma cell lines. We also preliminarily observed a synergistic effect of combination treatment comprising TMZ and a telomerase inhibitor in vitro. We identified six genes (MROH8, BET1, PTPRN2, STC1, NKX3-1, and ARMC10) using the random survival forests variable hunting algorithm based on the minimum error rate of the gene combination and constructed a gene...Continue Reading

References

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Methods Mentioned

BETA
RNA-seq

Software Mentioned

R
timeROC
survminer
GESA
pheatmap
GSEA
ClusterProfiler
ggplot2
rms
Gene Set Enrichment Analysis

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