Reduced Intestinal Epithelial GPX4 Expression Predicts Postoperative Crohn’s Disease Recurrence and Offers a Novel Therapeutic Target

Introduction: The Challenge of Postoperative Crohn’s Disease Management

Crohn’s disease (CD) is a chronic inflammatory condition characterized by transmural inflammation that can affect any part of the gastrointestinal tract. Despite significant advances in biological therapies, a substantial proportion of patients eventually require ileocolonic resection (ICR) due to complications such as strictures, fistulas, or medically refractory disease. However, surgery is rarely curative. Postoperative recurrence is a major clinical hurdle, with endoscopic recurrence rates reported as high as 70-90% within one year of surgery if no prophylactic treatment is administered.

Currently, clinicians rely on clinical risk factors—such as smoking status, previous resections, and penetrating disease phenotype—to stratify patients for postoperative prophylactic therapy. Yet, these factors often lack the precision required for personalized management. The Rutgeerts score remains the gold standard for assessing endoscopic recurrence at 6 to 12 months post-surgery, but it is a reactive rather than a predictive tool. There is an urgent unmet medical need for biomarkers that can be assessed at the time of resection to predict which patients are at the highest risk of early recurrence, thereby allowing for early, targeted intervention.