Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Cancer Epidemiol Biomarkers Prev. 2012 Dec;21(12):2176-84. doi: 10.1158/1055-9965.EPI-12-0745. Epub 2012 Oct 3.
Epidemiologic studies have reported that frequent consumption of quercetin-rich foods is inversely associated with lung cancer incidence. A quercetin-rich diet might modulate microRNA (miR) expression; however, this mechanism has not been fully examined.
miR expression data were measured by a custom-made array in formalin-fixed paraffin-embedded tissue samples from 264 lung cancer cases (144 adenocarcinomas and 120 squamous cell carcinomas). Intake of quercetin-rich foods was derived from a food-frequency questionnaire. In individual-miR-based analyses, we compared the expression of miRs (n = 198) between lung cancer cases consuming high versus low quercetin-rich food intake using multivariate ANOVA tests. In family-miR-based analyses, we used Functional Class Scoring (FCS) to assess differential effect on biologically functional miR families. We accounted for multiple testing using 10,000 global permutations (significance at P(global) < 0.10). All multivariate analyses were conducted separately by histology and by smoking status (former and current smokers).
Family-based analyses showed that a quercetin-rich diet differentiated miR expression profiles of the tumor suppressor let-7 family among adenocarcinomas (P(FCS) < 0.001). Other significantly differentiated miR families included carcinogenesis-related miR-146, miR-26, and miR-17 (P (FCS) < 0.05). In individual-based analyses, we found that among former and current smokers with adenocarcinoma, 33 miRs were observed to be differentiated between highest and lowest quercetin-rich food consumers (23 expected by chance; P(global) = 0.047).
We observed differential expression of key biologically functional miRs between high versus low consumers of quercetin-rich foods in adenocarcinoma cases.
Our findings provide preliminary evidence on the mechanism underlying quercetin-related lung carcinogenesis.
流行病学研究报告称，经常食用富含槲皮素的食物与肺癌发病率呈负相关。富含槲皮素的饮食可能会调节 microRNA（miR）的表达；然而，这种机制尚未得到充分研究。
通过定制的微阵列在 264 例肺癌病例（144 例腺癌和 120 例鳞状细胞癌）的福尔马林固定石蜡包埋组织样本中测量 miR 表达数据。通过食物频率问卷得出富含槲皮素食物的摄入量。在个体-miR 为基础的分析中，我们使用多变量方差分析比较了高槲皮素摄入和低槲皮素摄入的肺癌病例之间（n = 198）miRs 的表达。在家族-miR 为基础的分析中，我们使用功能分类评分（FCS）来评估对生物功能 miR 家族的差异影响。我们使用 10000 次全局置换进行了多次检验（P(global) < 0.10 时有统计学意义）。所有多变量分析均按组织学和吸烟状态（既往吸烟者和现吸烟者）进行。
家族分析显示，富含槲皮素的饮食可区分腺癌中肿瘤抑制因子 let-7 家族的 miR 表达谱（P(FCS) < 0.001）。其他显著分化的 miR 家族包括与致癌作用相关的 miR-146、miR-26 和 miR-17（P (FCS) < 0.05）。在个体分析中，我们发现，在腺癌的既往吸烟者和现吸烟者中，在槲皮素摄入最高和最低的两组中，有 33 个 miR 被观察到存在差异（23 个为预期差异；P(global) = 0.047）。
我们观察到在腺癌病例中，富含槲皮素的食物摄入量高与低的个体之间关键的生物学功能 miR 的表达存在差异。
我们的研究结果为槲皮素相关肺癌发生的机制提供了初步证据。
