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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. LesniakEmail author
Clinical Study

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 Whites Glioma Retinoic acid metabolism Karnofsky performance score 

Notes

Funding

This work was funded by a grant from Northwestern Brain Tumor Institute (10044349) to M.W. and C.M.H., by a Mentored Clinical Scientist Research Career Development Award (K08CA155764) from National Institute of Health (NIH)/National Cancer Institute to C.M.H., by a National Cancer Institute Outstanding Investigator Award from NIH/National Cancer Institute to M.S.L. (R35CA197725) and by a grant from NIH/National Cancer Institute to M.S.L. (R01 NS087990). J.M. received fellowship from NIH/National Cancer Institute (1F32NS098737-01A1).

Compliance with ethical standards

Conflict of interest

The authors have declared no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

11060_2019_3110_MOESM1_ESM.pdf (79 kb)
Supplementary material 1 (PDF 79 KB)
11060_2019_3110_MOESM2_ESM.pdf (662 kb)
Supplementary material 2 (PDF 662 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurological SurgeryNorthwestern UniversityChicagoUSA
  2. 2.Northwestern Memorial HospitalChicagoUSA

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