Race influences survival in glioblastoma patients with KPS ≥ 80 and associates with genetic markers of retinoic acid metabolism
To study whether the clinical outcome and molecular biology of gliomas in African-American patients fundamentally differ from those occurring in Whites.
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.
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).
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.
KeywordsAfrican Americans Whites Glioma Retinoic acid metabolism Karnofsky performance score
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.
This article does not contain any studies with human participants or animals performed by any of the authors.
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