Department of Neurological Surgery, Northwestern University, Chicago, IL, USA.
Northwestern Memorial Hospital, 676 N St. Clair, Suite 2210, Chicago, IL, 60611, USA.
J Neurooncol. 2019 Apr;142(2):375-384. doi: 10.1007/s11060-019-03110-5. Epub 2019 Jan 31.
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.
研究非裔美国患者的胶质瘤临床结果和分子生物学是否与白人患者的存在根本差异。
从癌症基因组图谱（TCGA）下载临床信息和分子谱（包括基因表达阵列、非沉默体细胞突变、DNA 甲基化和蛋白质表达）。还从西北医学企业数据仓库（NMEDW）提取电子病历进行分析。所有纳入 II-IV 级胶质瘤患者。
TCGA 分析了 931 名白人患者和 64 名非裔美国胶质瘤患者。非裔美国患者的卡诺夫斯基表现评分（KPS）≥80 与类似的白人 IV 级胶质母细胞瘤（GBM）患者相比，死亡风险显著降低[风险比（95%置信区间）=0.47（0.23，0.98），P=0.0444，C 指数=0.68]。因此，我们进一步比较了非裔美国 GBM 患者和 KPS≥80 的白人患者之间的基因表达谱。推断与非裔美国患者生存增加相关的基因谱揭示了一组 13 个可能与这种关联相关的基因，包括先前鉴定为非裔美国乳腺癌和结肠癌患者表达增加的基因（例如 CRYBB2）。此外，基因集富集分析显示，视黄酸（RA）代谢途径在比白人患者存活时间更长的非裔美国 GBM 患者中显著上调（Z 分数=-2.10，调整后 P 值=0.0449）。
非裔美国人的胶质瘤存活时间延长，仅受初始 KPS 评分影响。先前与癌症种族差异相关的基因和与 RA 代谢相关的途径可能在胶质瘤发病机制中发挥重要作用。未来对这些基因和途径的探索可能为这种无法治愈的疾病提供新的治疗方法。
