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J Neurol Surg A Cent Eur Neurosurg 2019; 80(04): 240-249
DOI: 10.1055/s-0039-1683448
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Integrated Transcriptomic Analysis of Necrosis-related Gene in Diffuse Gliomas

Jiajia Wang
1   Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Jie Ma
1   Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
› Author Affiliations Funding The authors gratefully acknowledge financial support from the National Natural Science Foundation of China (81271382).
Further Information

Publication History

22 July 2018

19 November 2018

Publication Date:
01 April 2019 (online)

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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

Supplementary Material

 

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