短非编码 RNA 作为从未分类炎症性肠病发展为克罗恩病或溃疡性结肠炎的预测生物标志物。
Short noncoding RNAs as predictive biomarkers for the development from inflammatory bowel disease unclassified to Crohn's disease or ulcerative colitis.
机构信息
Department of Pathology, Herlev University Hospital, Herlev, Denmark.
Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
出版信息
PLoS One. 2024 Feb 26;19(2):e0297353. doi: 10.1371/journal.pone.0297353. eCollection 2024.
Numerous pathogenic processes are mediated by short noncoding RNAs (sncRNA). Twenty percent of inflammatory bowel disease (IBD) patients are labelled as IBD unclassified (IBDU) at disease onset. Most IBDU patients are reclassified as Crohn's disease (CD) or ulcerative colitis (UC) within few years. Since the therapeutic methods for CD and UC differ, biomarkers that can forecast the categorization of IBDU into CD or UC are highly desired. Here, we investigated whether sncRNAs can predict CD or UC among IBDU patients. 35 IBDU patients who were initially diagnosed with IBDU were included in this retrospective investigation; of them, 12, 15, and 8 were reclassified into CD (IBDU-CD), UC (IBDU-UC), or remained as IBDU (IBDU-IBDU), respectively. Eight IBD patients, were included as references. SncRNA profiling on RNA from mucosal biopsies were performed using Affymetrix miRNA 4.0 array. Selected probe sets were validated using RT-qPCR. Among all patients and only adults, 306 and 499 probe sets respectively were differentially expressed between IBDU-CD and IBDU-UC. Six of the probe sets were evaluated by RT-qPCR, of which miR-182-5p, miR-451a and ENSG00000239080 (snoU13) together with age and sex resulted in an AUC of 78.6% (95% CI: 60-97) in discriminating IBDU-CD from IBDU-UC. Based on the three sncRNAs profile it is possible to predict if IBDU patients within 3 years will be reclassified as CD or UC. We showed that the expression profile of IBDU patients differ from that of definite CD or UC, suggesting that a subgroup of IBDU patients may compose a third unique IBD subtype.
大量的致病过程是由短链非编码 RNA(sncRNA)介导的。在疾病发作时,有 20%的炎症性肠病(IBD)患者被归类为未分类的 IBD(IBDU)。大多数 IBDU 患者在几年内被重新归类为克罗恩病(CD)或溃疡性结肠炎(UC)。由于 CD 和 UC 的治疗方法不同,因此非常需要能够预测 IBDU 分类为 CD 或 UC 的生物标志物。在这里,我们研究了 sncRNA 是否可以预测 IBDU 患者中的 CD 或 UC。这项回顾性研究纳入了 35 名最初被诊断为 IBDU 的 IBDU 患者;其中 12 名、15 名和 8 名患者分别被重新归类为 CD(IBDU-CD)、UC(IBDU-UC)或仍为 IBDU(IBDU-IBDU)。8 名 IBD 患者被纳入对照组。使用 Affymetrix miRNA 4.0 阵列对粘膜活检的 RNA 进行 sncRNA 谱分析。使用 RT-qPCR 验证选定的探针集。在所有患者和仅成人中,IBDU-CD 和 IBDU-UC 之间分别有 306 个和 499 个探针集差异表达。通过 RT-qPCR 评估了 6 个探针集,其中 miR-182-5p、miR-451a 和 ENSG00000239080(snoU13)与年龄和性别一起可将 IBDU-CD 与 IBDU-UC 区分开来,AUC 为 78.6%(95%CI:60-97)。基于这三个 sncRNA 谱,可以预测 IBDU 患者在 3 年内是否会重新归类为 CD 或 UC。我们发现 IBDU 患者的表达谱与明确的 CD 或 UC 不同,这表明 IBDU 患者的亚组可能构成第三种独特的 IBD 亚型。