Validated gene expression biomarker analysis for biopsy-based clinical trials in ulcerative colitis.
Validated gene expression biomarker analysis for biopsy-based clinical trials in ulcerative colitis.
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经验证的基因表达生物标志物分析用于溃疡性结肠炎基于活检的临床试验。
DOI：
10.1111/apt.12862
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发表时间：
2014
影响因子：
7.6
通讯作者：
Chang,JT
中科院分区：
文献类型：
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作者：
Boland,BS;Boyle,DL;Sandborn,WJ;Firestein,GS;Levesque,BG;Hillman,J;Zhang,B;Proudfoot,J;Eckmann,L;Ernst,PB;Rivera-Nieves,J;Pola,S;Copur-Dahi,N;Chang,JT
准确和可重复地测量溃疡性结肠炎（UC）患者结肠活检组织中促炎细胞因子的表达对于概念验证和作用机制研究至关重要。很少有研究已经严格建立了活检所需的准确和可重复的生物标志物measurement.AimTo验证方法测量结肠活检samples.MethodsTwelve基因表达的变化，结肠活检标本的数量从每个6个健康对照，6例患者与非活动性UC和7例患者与活动性UC。将马约内镜评分用作临床参考标准。定量PCR用于评估8个已知炎症基因的mRNA表达。功率检测减少基因表达的活动与非活动UC计算使用线性混合效应model.ResultsmRNA分析结肠活检是一个敏感和可行的方法，用于测量炎症基因表达的结肠活检。对于大多数基因，需要2 - 4例患者的3次直肠活检来检测对应于活动期与非活动期UC的基因表达变化，以达到80%的功效，α为0.05。结论我们的数据表明，系统测量mRNA水平的炎症生物标志物可以作为一种有价值的假设检验工具，以及溃疡性结肠炎的临床活性和对治疗的反应的评估。
BackgroundAccurate and reproducible measurement of expression of pro‐inflammatory cytokines in colonic biopsies from patients with ulcerative colitis (UC) is essential for proof‐of‐concept and mechanism‐of‐action studies. Few studies have rigorously established the number of biopsies required for accurate and reproducible biomarker measurements.AimTo validate methods for measuring changes in gene expression in colonic biopsy samples.MethodsTwelve colonic biopsies were obtained from each of six healthy controls, six patients with inactive UC and seven patients with active UC. Mayo endoscopic scores were used as a clinical reference standard. Quantitative PCR was used to assess mRNA expression of eight known inflammatory genes. The power to detect a reduction in gene expression in active vs. inactive UC was calculated using a linear mixed effect model.ResultsmRNA analysis of colonic biopsies is a sensitive and feasible approach for measuring inflammatory gene expression in colonic biopsies. Inflammatory biomarkers correlate with Mayo endoscopic subscores for each colonic region.For most genes, three rectal biopsies from two to four patients are required to detect changes in gene expression corresponding to active vs. inactive UC to achieve a power of 80% with an alpha of 0.05.ConclusionOur data suggest that systematic measurement of inflammatory biomarkers at the mRNA level can be a valuable tool for hypothesis testing, and assessment of clinical activity and response to therapy in ulcerative colitis.