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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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