Characterization of molecular response to Golimumab in Ulcerative Colitis by mucosal biopsy mRNA expression profiling: results from PURSUIT-SC induction study

To evaluate the effects of induction treatment with an anti-TNF, golimumab (GLM), on gene expression in patients with moderately to severely active ulcerative colitis (UC), we performed mRNA microarray studies on colon biopsies from patients who participated in the PURSUIT-SC induction study and additional samples from 21 healthy subjects. Comparisons were conducted between baseline UC (n=87) and healthy (n=21), and week 6 (n=75) vs. baseline (n=87) prior to treatment. A significant difference was observed in mRNA expression between UC and healthy. Significant expression modulations were identified in patients who responded to GLM at week 6, but not GLM-treated non-responders or placebo-treated subjects. Mucosal biopsy samples (162 UC from the PURSUIT-SC induction study and 21 healthy) were collected for RNA extraction and microarray analysis.

为评估抗TNF（anti-TNF）制剂戈利木单抗（golimumab, GLM）诱导治疗对中重度活动性溃疡性结肠炎（ulcerative colitis, UC）患者基因表达的影响，我们对参与PURSUIT-SC诱导研究的患者的结肠活检样本，以及21名健康受试者的额外样本开展了mRNA微阵列（mRNA microarray）研究。本研究分别开展了基线溃疡性结肠炎患者（n=87）与健康受试者（n=21）的对照，以及治疗前基线组（n=87）与第6周组（n=75）的对照。结果观察到，溃疡性结肠炎患者与健康受试者的mRNA表达存在显著差异；在第6周对戈利木单抗产生应答的患者中，鉴定出了显著的表达调控变化，而接受戈利木单抗治疗的无应答者或接受安慰剂治疗的受试者则未出现此类变化。本研究共收集黏膜活检样本（含来自PURSUIT-SC诱导研究的162份溃疡性结肠炎样本与21份健康样本）用于RNA提取及微阵列分析。