Noninvasive detection of candidate molecular biomarkers in subjects with a history of insulin resistance and colorectal adenomas.
Noninvasive detection of candidate molecular biomarkers in subjects with a history of insulin resistance and colorectal adenomas.
复制标题
对有胰岛素抵抗和结直肠腺瘤病史的受试者进行候选分子生物标志物的无创检测。
DOI：
10.1158/1940-6207.capr-08-0233
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Chapkin,RobertS
中科院分区：
文献类型：
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作者：
Zhao,Chen;Ivanov,Ivan;Dougherty,EdwardR;Hartman,TerrylJ;Lanza,Elaine;Bobe,Gerd;Colburn,NancyH;Lupton,JoanneR;Davidson,LaurieA;Chapkin,RobertS
我们开发了新的分子方法，使用含有完整脱落结肠细胞的粪便样本来量化结肠基因表达谱。在这项研究中，我们的目标是确定诊断基因集（组合），以对不同表型进行非侵入性分类。为此，在具有四种可能的危险因素组合（包括胰岛素抵抗和腺瘤性息肉病史）的受试者中评估了富含豆类、低血糖指数、高可发酵纤维饮食的效果。在一项随机交叉设计对照喂养研究中，每位参与者（总共 23 人；每组 5-12 人）食用实验饮食（1.5 杯煮熟的干豆）和对照饮食（等热量的美国平均饮食）4 周，饮食之间有 3 周的冲洗期。使用先前的生物学知识，降低了特征选择的复杂性，以对大小为 3 的所有允许的特征（基因）集执行详尽的搜索，其中 27 个的（无偏）误差估计为 0.15 或更小。线性判别分析已成功用于识别最佳单基因和两到三基因组合，以区分患有胰岛素抵抗、息肉病史或接触富含化学保护豆类饮食的受试者。这些结果支持我们的假设，即从粪便中分离的基因产物 (RNA) 在评估结肠癌风险方面具有诊断价值。
We have developed novel molecular methods using a stool sample, which contains intact sloughed colon cells, to quantify colonic gene expression profiles. In this study, our goal was to identify diagnostic gene sets (combinations) for the noninvasive classification of different phenotypes. For this purpose, the effects of a legume-enriched, low glycemic index, high fermentable fiber diet was evaluated in subjects with four possible combinations of risk factors, including insulin resistance and a history of adenomatous polyps. In a randomized crossover design controlled feeding study, each participant (a total of 23; 5–12 per group) consumed the experimental diet (1.5 cups of cooked dry beans) and a control diet (isocaloric average American diet) for 4 weeks with a 3-week washout period between diets. Using prior biological knowledge, the complexity of feature selection was reduced to perform an exhaustive search on all allowable feature (gene) sets of size 3, and among these, 27 had (unbiased) error estimates of 0.15 or less. Linear discriminant analysis was successfully used to identify the best single genes and two- to three-gene combinations for distinguishing subjects with insulin resistance, a history of polyps, or exposure to a chemoprotective legume-rich diet. These results support our premise that gene products (RNA) isolated from stool have diagnostic value in terms of assessing colon cancer risk.