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June 14, 2016; 86 (24) Article

Bioinformatic profiling identifies an immune-related risk signature for glioblastoma

Wen Cheng, Xiufang Ren, Chuanbao Zhang, Jinquan Cai, Yang Liu, Sheng Han, Anhua Wu
First published May 25, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002770
Wen Cheng
From the Department of Neurosurgery (W.C., Y.L., S.H., A.W.), The First Hospital of China Medical University; Department of Pathology (X.R.), Shengjing Hospital of China Medical University, Shenyang; Beijing Neurosurgical Institute (C.Z.), Capital Medical University; and Department of Neurosurgery (J.C.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
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Xiufang Ren
From the Department of Neurosurgery (W.C., Y.L., S.H., A.W.), The First Hospital of China Medical University; Department of Pathology (X.R.), Shengjing Hospital of China Medical University, Shenyang; Beijing Neurosurgical Institute (C.Z.), Capital Medical University; and Department of Neurosurgery (J.C.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
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Chuanbao Zhang
From the Department of Neurosurgery (W.C., Y.L., S.H., A.W.), The First Hospital of China Medical University; Department of Pathology (X.R.), Shengjing Hospital of China Medical University, Shenyang; Beijing Neurosurgical Institute (C.Z.), Capital Medical University; and Department of Neurosurgery (J.C.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
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Jinquan Cai
From the Department of Neurosurgery (W.C., Y.L., S.H., A.W.), The First Hospital of China Medical University; Department of Pathology (X.R.), Shengjing Hospital of China Medical University, Shenyang; Beijing Neurosurgical Institute (C.Z.), Capital Medical University; and Department of Neurosurgery (J.C.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
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Yang Liu
From the Department of Neurosurgery (W.C., Y.L., S.H., A.W.), The First Hospital of China Medical University; Department of Pathology (X.R.), Shengjing Hospital of China Medical University, Shenyang; Beijing Neurosurgical Institute (C.Z.), Capital Medical University; and Department of Neurosurgery (J.C.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
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Sheng Han
From the Department of Neurosurgery (W.C., Y.L., S.H., A.W.), The First Hospital of China Medical University; Department of Pathology (X.R.), Shengjing Hospital of China Medical University, Shenyang; Beijing Neurosurgical Institute (C.Z.), Capital Medical University; and Department of Neurosurgery (J.C.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
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Anhua Wu
From the Department of Neurosurgery (W.C., Y.L., S.H., A.W.), The First Hospital of China Medical University; Department of Pathology (X.R.), Shengjing Hospital of China Medical University, Shenyang; Beijing Neurosurgical Institute (C.Z.), Capital Medical University; and Department of Neurosurgery (J.C.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
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Citation
Bioinformatic profiling identifies an immune-related risk signature for glioblastoma
Wen Cheng, Xiufang Ren, Chuanbao Zhang, Jinquan Cai, Yang Liu, Sheng Han, Anhua Wu
Neurology Jun 2016, 86 (24) 2226-2234; DOI: 10.1212/WNL.0000000000002770

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Abstract

Objective: To investigate the local immune status and its prognostic value in glioma.

Methods: A cohort of 297 glioma samples with whole genome microarray expression data from the Chinese Glioma Genome Atlas database were included for discovery. The Cancer Genome Atlas (TCGA) database was used for validation. Principal components analysis and gene set enrichment analysis were used to explore the bioinformatic implication.

Results: Distinct local immune status was identified according to histologic grade. Glioblastoma (GBM) exhibited an enhanced immune phenotype compared to lower grade glioma. We profiled the immune-related gene set and identified 8 genes (FOXO3, IL6, IL10, ZBTB16, CCL18, AIMP1, FCGR2B, and MMP9) with the greatest prognostic value in GBM. A local immune-related risk signature was developed from the genes to distinguish cases as high or low risk of unfavorable prognosis, which could be validated in TCGA database. High-risk patients conferred an enhanced intensity of local immune response compared to low-risk ones. Additionally, the signature exhibited different distribution based on molecular features. The signature had prognostic significance in the stratified cohorts and was identified as an independent prognostic factor for GBM.

Conclusions: We profiled the immune status in glioma and established a local immune signature for GBM, which could independently identify patients with a high risk of reduced survival, indicating the relationship between prognosis and local immune response.

GLOSSARY

CGGA=
Chinese Glioma Genome Atlas;
CI=
confidence interval;
GBM=
glioblastoma;
GSEA=
gene set enrichment analysis;
HR=
hazard ratio;
LGG=
lower grade glioma;
MAD=
median absolute deviation;
OS=
overall survival;
PFS=
progression-free survival;
sGBM=
secondary glioblastoma;
TCGA=
The Cancer Genome Atlas

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 2220

  • Supplemental data at Neurology.org

  • Received November 8, 2015.
  • Accepted in final form February 21, 2016.
  • © 2016 American Academy of Neurology
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