Race influences survival in glioblastoma patients with KPS ≥ 80 and associates with genetic markers of retinoic acid metabolism

Meijing Wu, Jason Michael Miska, Ting Xiao, Peng Zhang, J. Robert Kane, Irina V Balyasnikova, James P Chandler, Craig Michael Horbinski, Maciej S Lesniak*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose: To study whether the clinical outcome and molecular biology of gliomas in African-American patients fundamentally differ from those occurring in Whites. Methods: The clinical information and molecular profiles (including gene expression array, non-silent somatic mutation, DNA methylation and protein expression) were downloaded from The Cancer genome atlas (TCGA). Electronic medical records were abstracted from Northwestern Medicine Enterprise Data Warehouse (NMEDW) for analysis as well. Grade II–IV Glioma patients were all included. Results: 931 Whites and 64 African-American glioma patients from TCGA were analyzed. African-American with Karnofsky performance score (KPS) ≥ 80 have significantly lower risk of death than similar white Grade IV Glioblastoma (GBM) patients [HR (95% CI) = 0.47 (0.23, 0.98), P = 0.0444, C-index = 0.68]. Therefore, we further compared gene expression profiles between African-American GBM patients and Whites with KPS ≥ 80. Extrapolation of genes significantly associated with increased African-American patient survival revealed a set of 13 genes with a possible role in this association, including elevated expression of genes previously identified as increased in African-American breast and colon cancer patients (e.g. CRYBB2). Furthermore, gene set enrichment analysis revealed retinoic acid (RA) metabolism as a pathway significantly upregulated in African-American GBM patients who survive longer than Whites (Z-score = − 2.10, Adjusted P-value = 0.0449). Conclusions: African Americans have prolonged survival with glioma which is influenced only by initial KPS score. Genes previously associated with both racial disparities in cancer and pathways associated with RA metabolism may play an important role in glioma etiology. In the future exploration of these genes and pathways may inform novel therapies for this incurable disease.

Original languageEnglish (US)
Pages (from-to)375-384
Number of pages10
JournalJournal of Neuro-Oncology
Volume142
Issue number2
DOIs
StatePublished - Apr 15 2019

Fingerprint

Glioblastoma
Tretinoin
Genetic Markers
African Americans
Glioma
Survival
Atlases
Genes
Transcriptome
Genome
Neoplasms
Electronic Health Records
DNA Methylation
Colonic Neoplasms
Molecular Biology
Medicine
Breast Neoplasms
Gene Expression
Mutation

Keywords

  • African Americans
  • Glioma
  • Karnofsky performance score
  • Retinoic acid metabolism
  • Whites

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

@article{856c3e6e78234e629fe2f49abd7ba1d2,
title = "Race influences survival in glioblastoma patients with KPS ≥ 80 and associates with genetic markers of retinoic acid metabolism",
abstract = "Purpose: To study whether the clinical outcome and molecular biology of gliomas in African-American patients fundamentally differ from those occurring in Whites. Methods: The clinical information and molecular profiles (including gene expression array, non-silent somatic mutation, DNA methylation and protein expression) were downloaded from The Cancer genome atlas (TCGA). Electronic medical records were abstracted from Northwestern Medicine Enterprise Data Warehouse (NMEDW) for analysis as well. Grade II–IV Glioma patients were all included. Results: 931 Whites and 64 African-American glioma patients from TCGA were analyzed. African-American with Karnofsky performance score (KPS) ≥ 80 have significantly lower risk of death than similar white Grade IV Glioblastoma (GBM) patients [HR (95{\%} CI) = 0.47 (0.23, 0.98), P = 0.0444, C-index = 0.68]. Therefore, we further compared gene expression profiles between African-American GBM patients and Whites with KPS ≥ 80. Extrapolation of genes significantly associated with increased African-American patient survival revealed a set of 13 genes with a possible role in this association, including elevated expression of genes previously identified as increased in African-American breast and colon cancer patients (e.g. CRYBB2). Furthermore, gene set enrichment analysis revealed retinoic acid (RA) metabolism as a pathway significantly upregulated in African-American GBM patients who survive longer than Whites (Z-score = − 2.10, Adjusted P-value = 0.0449). Conclusions: African Americans have prolonged survival with glioma which is influenced only by initial KPS score. Genes previously associated with both racial disparities in cancer and pathways associated with RA metabolism may play an important role in glioma etiology. In the future exploration of these genes and pathways may inform novel therapies for this incurable disease.",
keywords = "African Americans, Glioma, Karnofsky performance score, Retinoic acid metabolism, Whites",
author = "Meijing Wu and Miska, {Jason Michael} and Ting Xiao and Peng Zhang and Kane, {J. Robert} and Balyasnikova, {Irina V} and Chandler, {James P} and Horbinski, {Craig Michael} and Lesniak, {Maciej S}",
year = "2019",
month = "4",
day = "15",
doi = "10.1007/s11060-019-03110-5",
language = "English (US)",
volume = "142",
pages = "375--384",
journal = "Journal of Neuro-Oncology",
issn = "0167-594X",
publisher = "Kluwer Academic Publishers",
number = "2",

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TY - JOUR

T1 - Race influences survival in glioblastoma patients with KPS ≥ 80 and associates with genetic markers of retinoic acid metabolism

AU - Wu, Meijing

AU - Miska, Jason Michael

AU - Xiao, Ting

AU - Zhang, Peng

AU - Kane, J. Robert

AU - Balyasnikova, Irina V

AU - Chandler, James P

AU - Horbinski, Craig Michael

AU - Lesniak, Maciej S

PY - 2019/4/15

Y1 - 2019/4/15

N2 - Purpose: To study whether the clinical outcome and molecular biology of gliomas in African-American patients fundamentally differ from those occurring in Whites. Methods: The clinical information and molecular profiles (including gene expression array, non-silent somatic mutation, DNA methylation and protein expression) were downloaded from The Cancer genome atlas (TCGA). Electronic medical records were abstracted from Northwestern Medicine Enterprise Data Warehouse (NMEDW) for analysis as well. Grade II–IV Glioma patients were all included. Results: 931 Whites and 64 African-American glioma patients from TCGA were analyzed. African-American with Karnofsky performance score (KPS) ≥ 80 have significantly lower risk of death than similar white Grade IV Glioblastoma (GBM) patients [HR (95% CI) = 0.47 (0.23, 0.98), P = 0.0444, C-index = 0.68]. Therefore, we further compared gene expression profiles between African-American GBM patients and Whites with KPS ≥ 80. Extrapolation of genes significantly associated with increased African-American patient survival revealed a set of 13 genes with a possible role in this association, including elevated expression of genes previously identified as increased in African-American breast and colon cancer patients (e.g. CRYBB2). Furthermore, gene set enrichment analysis revealed retinoic acid (RA) metabolism as a pathway significantly upregulated in African-American GBM patients who survive longer than Whites (Z-score = − 2.10, Adjusted P-value = 0.0449). Conclusions: African Americans have prolonged survival with glioma which is influenced only by initial KPS score. Genes previously associated with both racial disparities in cancer and pathways associated with RA metabolism may play an important role in glioma etiology. In the future exploration of these genes and pathways may inform novel therapies for this incurable disease.

AB - Purpose: To study whether the clinical outcome and molecular biology of gliomas in African-American patients fundamentally differ from those occurring in Whites. Methods: The clinical information and molecular profiles (including gene expression array, non-silent somatic mutation, DNA methylation and protein expression) were downloaded from The Cancer genome atlas (TCGA). Electronic medical records were abstracted from Northwestern Medicine Enterprise Data Warehouse (NMEDW) for analysis as well. Grade II–IV Glioma patients were all included. Results: 931 Whites and 64 African-American glioma patients from TCGA were analyzed. African-American with Karnofsky performance score (KPS) ≥ 80 have significantly lower risk of death than similar white Grade IV Glioblastoma (GBM) patients [HR (95% CI) = 0.47 (0.23, 0.98), P = 0.0444, C-index = 0.68]. Therefore, we further compared gene expression profiles between African-American GBM patients and Whites with KPS ≥ 80. Extrapolation of genes significantly associated with increased African-American patient survival revealed a set of 13 genes with a possible role in this association, including elevated expression of genes previously identified as increased in African-American breast and colon cancer patients (e.g. CRYBB2). Furthermore, gene set enrichment analysis revealed retinoic acid (RA) metabolism as a pathway significantly upregulated in African-American GBM patients who survive longer than Whites (Z-score = − 2.10, Adjusted P-value = 0.0449). Conclusions: African Americans have prolonged survival with glioma which is influenced only by initial KPS score. Genes previously associated with both racial disparities in cancer and pathways associated with RA metabolism may play an important role in glioma etiology. In the future exploration of these genes and pathways may inform novel therapies for this incurable disease.

KW - African Americans

KW - Glioma

KW - Karnofsky performance score

KW - Retinoic acid metabolism

KW - Whites

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U2 - 10.1007/s11060-019-03110-5

DO - 10.1007/s11060-019-03110-5

M3 - Article

VL - 142

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JO - Journal of Neuro-Oncology

JF - Journal of Neuro-Oncology

SN - 0167-594X

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