Abstract
Glioblastoma multiforme (GBM), an aggressive brain tumor, is characterized histologically
by the presence of a necrotic center surrounded by so-called pseudopalisading cells.
Pseudopalisading necrosis has long been used as a prognostic feature. However, the
underlying molecular mechanism regulating the progression of GBMs remains unclear.
We hypothesized that the gene expression profiles of individual cancers, specifically
necrosis-related genes, would provide objective information that would allow for the
creation of a prognostic index. Gene expression profiles of necrotic and nonnecrotic
areas were obtained from the Ivy Glioblastoma Atlas Project (IVY GAP) database to
explore the differentially expressed genes.
A robust signature of seven genes was identified as a predictor for glioblastoma and
low-grade glioma (GBM/LGG) in patients from The Cancer Genome Atlas (TCGA) cohort.
This set of genes was able to stratify GBM/LGG and GBM patients into high-risk and
low-risk groups in the training set as well as the validation set. The TCGA, Repository
for Molecular Brain Neoplasia Data (Rembrandt), and GSE16011 databases were then used
to validate the expression level of these seven genes in GBMs and LGGs. Finally, the
differentially expressed genes (DEGs) in the high-risk and low-risk groups were subjected
to gene ontology enrichment, Kyoto Encyclopedia of Genes and Genomes pathway, and
gene set enrichment analyses, and they revealed that these DEGs were associated with
immune and inflammatory responses. In conclusion, our study identified a novel seven-gene
signature that may guide the prognostic prediction and development of therapeutic
applications.
Keywords
glioblastoma multiforme - necrosis - prognosis - IVY GAP - gene ontology - KEGG pathway
- GSEA analysis
