Crohn's disease (CD) is a debilitating gastrointestinal disorder that can impact the entirety of the GI tract. While substantial progress has been made in the medical management of CD, it remains incurable, frequently relapses, and is a significant financial and medical burden. The pathophysiology of CD is not well understood, but it is thought to arise in genetically susceptible individuals upon an environmental insult. Further elucidation of the disease etiology promises to expose additional therapeutic avenues, with the hope of reducing the burden of CD. One approach to understanding disease pathophysiology is to identify clinically relevant molecular disease subsets using transcriptomics. In this report, we use hierarchical clustering of the ileal transcriptomes of 34 patients and identify two CD subsets. Clinically, these clusters differed in the age of the patients at CD diagnosis, suggesting that age of onset impacts disease pathophysiology. The clusters were segregated by three major gene ontology categories: developmental processes, ion homeostasis, and the immune response. Of the genes constituting the immune system category, expression of extracellular matrix (ECM)-associated genes, COL4A1, S100A9, ADAMTS2, SERPINE1, and FCN1, exhibit the strongest correlation with an individual's age at CD diagnosis. Together these findings demonstrate that transcriptional profiling is a powerful approach to subclassify CD patients.

中文翻译：

---

对克罗恩病患者回肠组织的转录组学分析确定了细胞外基质基因，该基因可在诊断时按年龄区分个体。

克罗恩病（CD）是一种令人衰弱的胃肠道疾病，可影响整个胃肠道。尽管CD的医疗管理已取得实质性进展，但它仍然无法治愈，经常复发，并且是巨大的财务和医疗负担。CD的病理生理学尚未被很好地理解，但是认为它是在受到环境侵害后在遗传易感个体中产生的。对疾病病因的进一步阐明有望揭示更多的治疗途径，以期减轻CD负担。了解疾病病理生理学的一种方法是使用转录组学来鉴定临床相关的分子疾病亚群。在本报告中，我们使用34位患者的回肠转录组的分层聚类，并确定了两个CD亚组。临床上 这些簇在CD诊断时的患者年龄不同，这表明发病年龄会影响疾病的病理生理。这些簇按三个主要的基因本体分类：发育过程，离子稳态和免疫反应。在构成免疫系统类别的基因中，细胞外基质（ECM）相关基因，COL4A1，S100A9，ADAMTS2，SERPINE1和FCN1的表达与CD诊断时与年龄的关系最密切。这些发现共同表明，转录谱分析是将CD患者亚分类的有效方法。和免疫反应。在构成免疫系统类别的基因中，细胞外基质（ECM）相关基因，COL4A1，S100A9，ADAMTS2，SERPINE1和FCN1的表达与CD诊断时与年龄的关系最密切。这些发现共同表明，转录谱分析是将CD患者亚分类的有效方法。和免疫反应。在构成免疫系统类别的基因中，细胞外基质（ECM）相关基因，COL4A1，S100A9，ADAMTS2，SERPINE1和FCN1的表达与CD诊断时与年龄的关系最密切。这些发现共同表明，转录谱分析是将CD患者亚分类的有效方法。