Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
Clin Cancer Res. 2017 Dec 1;23(23):7412-7425. doi: 10.1158/1078-0432.CCR-17-0527.
To determine whether racial differences in gene and miRNA expression translates to differences in lung tumor biology with clinical relevance in African Americans (AAs) and European Americans (EAs). The NCI-Maryland Case Control Study includes seven Baltimore City hospitals and is overrepresented with AA patients (∼40%). Patients that underwent curative NSCLC surgery between 1998 and 2014 were enrolled. Comparative molecular profiling used mRNA ( = 22 AAs and 19 EAs) and miRNA ( = 42 AAs and 55 EAs) expression arrays to track differences in paired fresh frozen normal tissues and lung tumor specimens from AAs and EAs. Pathway enrichment, predicted drug response, tumor microenvironment infiltration, cancer immunotherapy antigen profiling, and miRNA target enrichment were assessed. AA-enriched differential gene expression was characterized by stem cell and invasion pathways. Differential gene expression in lung tumors from EAs was primarily characterized by cell proliferation pathways. Population-specific gene expression was partly driven by population-specific miRNA expression profiles. Drug susceptibility predictions revealed a strong inverse correlation between AA resistance and EA sensitivity to the same panel of drugs. Statistically significant differences in M1 and M2 macrophage infiltration were observed in AAs ( < 0.05); however, expression was similar between both. Comparative transcriptomic profiling revealed clear differences in lung tumor biology between AAs and EAs. Increased participation by AAs in lung cancer clinical trials are needed to integrate, and leverage, transcriptomic differences with other clinical information to maximize therapeutic benefit in both AAs and EAs. .
为了确定基因和 miRNA 表达的种族差异是否转化为非裔美国人和欧洲裔美国人（EAs）的临床相关肺肿瘤生物学差异。NCI-Maryland 病例对照研究包括巴尔的摩市的七家医院，非裔美国患者的比例过高（约 40%）。研究纳入了 1998 年至 2014 年间接受根治性 NSCLC 手术的患者。比较分子谱分析使用 mRNA（=22 个非裔美国人样本和 19 个欧洲裔美国人样本）和 miRNA（=42 个非裔美国人样本和 55 个欧洲裔美国人样本）表达谱来追踪非裔美国人和欧洲裔美国人配对的新鲜冷冻正常组织和肺肿瘤标本中的差异。评估了通路富集、预测药物反应、肿瘤微环境浸润、癌症免疫治疗抗原分析和 miRNA 靶基因富集。非裔美国人中富集的差异基因表达特征是干细胞和侵袭途径。欧洲裔美国人肺肿瘤中的差异基因表达主要由细胞增殖途径特征化。群体特异性基因表达部分由群体特异性 miRNA 表达谱驱动。药物敏感性预测显示，AA 耐药性和 EA 对同一组药物的敏感性之间存在很强的负相关。在非裔美国人中观察到 M1 和 M2 巨噬细胞浸润的统计学显著差异（<0.05）；然而，在两者之间， 表达相似。比较转录组分析揭示了非裔美国人和欧洲裔美国人之间肺肿瘤生物学的明显差异。需要增加非裔美国人参与肺癌临床试验，以整合和利用转录组差异与其他临床信息，最大限度地提高非裔美国人和欧洲裔美国人的治疗效果。
