Burakoff Robert, Pabby Vikas, Onyewadume Louisa, Odze Robert, Adackapara Cheryl, Wang Wei, Friedman Sonia, Hamilton Matthew, Korzenik Joshua, Levine Jonathan, Makrauer Frederick, Cheng Changming, Smith Hai Choo, Liew Choong-Chin, Chao Samuel
*Division of Gastroenterology and Hepatology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; †Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California; ‡Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts; §Sentinel Center, SBC, Shanghai, China; ‖GoldenHealthDx, Ontario, Canada; and ¶GeneNews, Toronto, Canada.
Inflamm Bowel Dis. 2015 May;21(5):1132-40. doi: 10.1097/MIB.0000000000000340.
Identifying specific genes that are differentially expressed during inflammatory bowel disease flares may help stratify disease activity. The aim of this study was to identify panels of genes to be able to distinguish disease activity in Crohn's disease (CD) and ulcerative colitis (UC).
Patients were grouped into categories based on disease and severity determined by histological grading. Whole blood was collected by PAXgene Blood RNA collection tubes, (PreAnalytiX) and gene expression analysis using messenger RNA was conducted. Logistic regression was performed on multiple combinations of common probe sets, and data were evaluated in terms of discrimination by computing the area under the receiving operator characteristic curve (ROC-AUC).
Nine inactive CD, 8 mild CD, 10 moderate-to-severe CD, 9 inactive UC, 8 mild UC, 10 moderate-to-severe UC, and 120 controls were hybridized to Affymetrix U133 Plus 2 microarrays. Panels of 6 individual genes discriminated the stages of disease activity: CD with mild severity {ROC-AUC, 0.89 (95% confidence interval [CI], 0.84%-0.95%)}, CD with moderate-to-severe severity (ROC-AUC 0.98 [95% CI, 0.97-1.0]), UC with mild severity (ROC-AUC 0.92 [95% CI, 0.87-0.96]), and UC with moderate-to-severe severity (ROC-AUC 0.99 [95% CI, 0.97-1.0]). Validation by real-time reverse transcription-PCR confirmed the Affymetrix microarray data.
The specific whole blood gene panels reliably distinguished CD and UC and determined the activity of disease, with high sensitivity and specificity in our cohorts of patients. This simple serological test has the potential to become a biomarker to determine the activity of disease.
识别在炎症性肠病发作期间差异表达的特定基因可能有助于对疾病活动进行分层。本研究的目的是确定能够区分克罗恩病（CD）和溃疡性结肠炎（UC）疾病活动的基因组合。
根据组织学分级确定的疾病和严重程度将患者分组。使用PAXgene Blood RNA采集管（PreAnalytiX）采集全血，并进行信使核糖核酸基因表达分析。对常见探针集的多种组合进行逻辑回归，并通过计算接受者操作特征曲线下面积（ROC-AUC）来评估数据的辨别力。
将9例非活动性CD、8例轻度CD、10例中度至重度CD、9例非活动性UC、8例轻度UC、10例中度至重度UC和120例对照与Affymetrix U133 Plus 2微阵列进行杂交。6个单个基因的组合能够区分疾病活动阶段：轻度严重程度的CD{ROC-AUC，0.89（95%置信区间[CI]，0.84%-0.95%）}，中度至重度严重程度的CD（ROC-AUC 0.98[95%CI，0.97-1.0]），轻度严重程度的UC（ROC-AUC 0.92[95%CI，0.87-0.96]），以及中度至重度严重程度的UC（ROC-AUC 0.99[95%CI，0.97-1.0]）。通过实时逆转录-聚合酶链反应进行的验证证实了Affymetrix微阵列数据。
特定的全血基因组合能够可靠地区分CD和UC，并确定疾病活动，在我们的患者队列中具有高敏感性和特异性。这种简单的血清学检测有可能成为确定疾病活动的生物标志物。
