Sare Verstockt1, Gert De Hertogh2,3, Jan Van der Goten4, Bram Verstockt4,5, Maaike Vancamelbeke4, Kathleen Machiels4, Leentje Van Lommel6, Frans Schuit6, Gert Van Assche4,5, Paul Rutgeerts4,5, Marc Ferrante4,5, Séverine Vermeire4,5, Ingrid Arijs4,7, Isabelle Cleynen1. 1. Laboratory for Complex Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium. 2. Department of Morphology and Molecular Pathology, University Hospitals, Leuven, Belgium. 3. Department of Imaging & Pathology, Translational Cell & Tissue Research, KU Leuven, Leuven, Belgium. 4. Translational Research Center for Gastrointestinal Disorders [TARGID], Department of Chronic Diseases, Metabolism & Aging [CHROMETA], KU Leuven, Leuven, Belgium. 5. Department of Gastroenterology and Hepatology, University Hospitals, KU Leuven, Leuven, Belgium. 6. Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium. 7. Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium; Jessa Hospital, Hasselt, Belgium.
Abstract
BACKGROUND AND AIMS: Early treatment of Crohn's disease [CD] is required in order to optimize patient outcomes. To this end, we need to gain a better understanding of the molecular changes at the onset of CD. METHODS: As a model for the earliest mucosal CD lesions, we study post-operative recurrent CD [Rutgeerts score ≥ i2b]. We are the first to analyse gene and microRNA [miRNA] expression profiles in ileal biopsies from these patients, and compare them with those of newly diagnosed [≤18 months] and late-stage [>10 years after diagnosis] CD patients. RESULTS: Except for one gene [WNT5A], there are no differential genes in CD patients without post-operative recurrence [i0], showing that previous disease did not influence gene expression in the neoterminal ileum, and that this model can be used to study early mucosal CD lesions. Gene expression and co-expression network dysregulation is more pronounced in newly diagnosed and late-stage CD than in post-operative recurrent CD, with most important modules associated with [a]granulocyte adhesion/diapedesis, and cholesterol biosynthesis. In contrast, we found a role for snoRNAs/miRNAs in recurrent CD, highlighting the potential importance of regulatory RNAs in early disease stages. Immunohistochemistry confirmed the expression of key dysregulated genes in damaged/regenerating epithelium and immune cells in recurrent CD. CONCLUSIONS: Aside from regulatory RNAs, there are no clear gene signatures separating post-operative recurrent, newly diagnosed, and late-stage CD. The relative contribution of dysregulated genes and networks differs, and suggests that surgery may reset the disease at the mucosal site, and therefore post-operative recurrent CD might be a good model a good model to study to study early mucosal CD lesions.
BACKGROUND AND AIMS: Early treatment of Crohn's disease [CD] is required in order to optimize patient outcomes. To this end, we need to gain a better understanding of the molecular changes at the onset of CD. METHODS: As a model for the earliest mucosal CD lesions, we study post-operative recurrent CD [Rutgeerts score ≥ i2b]. We are the first to analyse gene and microRNA [miRNA] expression profiles in ileal biopsies from these patients, and compare them with those of newly diagnosed [≤18 months] and late-stage [>10 years after diagnosis] CD patients. RESULTS: Except for one gene [WNT5A], there are no differential genes in CD patients without post-operative recurrence [i0], showing that previous disease did not influence gene expression in the neoterminal ileum, and that this model can be used to study early mucosal CD lesions. Gene expression and co-expression network dysregulation is more pronounced in newly diagnosed and late-stage CD than in post-operative recurrent CD, with most important modules associated with [a]granulocyte adhesion/diapedesis, and cholesterol biosynthesis. In contrast, we found a role for snoRNAs/miRNAs in recurrent CD, highlighting the potential importance of regulatory RNAs in early disease stages. Immunohistochemistry confirmed the expression of key dysregulated genes in damaged/regenerating epithelium and immune cells in recurrent CD. CONCLUSIONS: Aside from regulatory RNAs, there are no clear gene signatures separating post-operative recurrent, newly diagnosed, and late-stage CD. The relative contribution of dysregulated genes and networks differs, and suggests that surgery may reset the disease at the mucosal site, and therefore post-operative recurrent CD might be a good model a good model to study to study early mucosal CD lesions.
Authors: Ingunn Bakke; Gunnar Andreas Walaas; Torunn Bruland; Elin Synnøve Røyset; Atle van Beelen Granlund; Celia Escudero-Hernández; Silje Thorsvik; Andreas Münch; Arne Kristian Sandvik; Ann Elisabet Østvik Journal: J Gastroenterol Date: 2021-08-19 Impact factor: 7.527
Authors: Rong Lu; Yong-Guo Zhang; Yinglin Xia; Jilei Zhang; Arthur Kaser; Richard Blumberg; Jun Sun Journal: Gastroenterology Date: 2020-11-18 Impact factor: 22.682