Fujioka Shin, Nakamichi Ikuo, Esaki Motohiro, Asano Kouichi, Matsumoto Takayuki, Kitazono Takanari
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
J Gastroenterol Hepatol. 2014 Jun;29(6):1207-14. doi: 10.1111/jgh.12523.
microRNAs (miRNAs) have been suggested to be candidates for biomarkers in various diseases including Crohn's disease (CD). To identify possible biomarkers predictive of the therapeutic effect of infliximab in CD, we investigated serum miRNA levels during the induction therapy by the medication.
Nineteen CD patients who were applied to the induction therapy by infliximab were enrolled. Serum samples for miRNA analyses were obtained at weeks 0 and 6, and the therapeutic efficacy by infliximab was assessed according to the Crohn's disease activity index value at week 14. Exploratory miRNA profiling by low-density array was initially performed in three patients. The levels of candidate miRNA were subsequently determined by real-time polymerase chain reaction (PCR) assays in the remaining 16 patients. The miRNA levels during the induction therapy were compared between the two groups classified by the clinical response to infliximab at week 14.
Low-density array analysis identified 14 miRNAs that showed twofold or more altered expression during the induction therapy by infliximab. Subsequent analysis by real-time PCR demonstrated significantly increased levels of five miRNAs (let-7d, let-7e, miR-28-5p, miR-221, and miR-224) at week 6 when compared with those at week 0 (P < 0.05 each). In addition, miRNA levels of let-7d and let-7e were significantly increased in the group of patients who achieved clinical remission by infliximab (P = 0.001 and P = 0.002, respectively).
let-7d and let-7e might be possible therapeutic biomarkers in patients with CD, who are treated by infliximab.
微小RNA（miRNA）被认为是包括克罗恩病（CD）在内的多种疾病生物标志物的候选者。为了确定可预测英夫利昔单抗对CD治疗效果的潜在生物标志物，我们研究了用药诱导治疗期间血清miRNA水平。
纳入19例接受英夫利昔单抗诱导治疗的CD患者。在第0周和第6周采集用于miRNA分析的血清样本，并根据第14周的克罗恩病活动指数评估英夫利昔单抗的治疗效果。最初在3例患者中通过低密度阵列进行探索性miRNA谱分析。随后在其余16例患者中通过实时聚合酶链反应（PCR）测定候选miRNA的水平。比较第14周根据英夫利昔单抗临床反应分类的两组患者诱导治疗期间的miRNA水平。
低密度阵列分析鉴定出14种miRNA，其在英夫利昔单抗诱导治疗期间表达变化两倍或更多。随后的实时PCR分析显示，与第0周相比，第6周时5种miRNA（let-7d、let-7e、miR-28-5p、miR-221和miR-224）水平显著升高（各P<0.05）。此外，英夫利昔单抗实现临床缓解的患者组中let-7d和let-7e的miRNA水平显著升高（分别为P = 0.001和P = 0.002）。
let-7d和let-7e可能是接受英夫利昔单抗治疗的CD患者的潜在治疗生物标志物。
