Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy

• Published in: Pathology, research and practice Vol. 216; no. 6; p. 152945
• Main Authors: Stankovic, Biljana, Dragasevic, Sanja, Klaassen, Kristel, Kotur, Nikola, Srzentic Drazilov, Sanja, Zukic, Branka, Sokic Milutinovic, Aleksandra, Milovanovic, Tamara, Lukic, Snezana, Popovic, Dragan, Pavlovic, Sonja, Nikcevic, Gordana
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.06.2020
• Subjects: Adult; Apoptosis - genetics; Crohn Disease - pathology; Cytokines - genetics; Female; Humans; Ileal Crohn's disease; Inflammation - genetics; Inflammation - pathology; Intestinal Mucosa - pathology; Male; Middle Aged; Molecular profiling; Molecular Targeted Therapy; Mucosal phenotypes; Phenotype; Pilot Projects; Transcriptome; Young Adult; Ileal Crohn's disease; Molecular profiling; Mucosal phenotypes
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1016/j.prp.2020.152945

Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles. From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Bax, Fas and FasL) genes' expression levels by real-time PCR, while NFκB transcriptional potency was assessed by electromobility gel shift assay. Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Bax was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NFκB has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance. We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients.