Gene expression alterations in inflamed and unaffected colon mucosa from patients with mild inflammatory bowel disease

Xu,Lili; Ma,Lili; Lian,Jingjing; Yang,Jiayin; Chen,Shiyao

doi:10.3892/mmr.2016.4880

Gene expression alterations in inflamed and unaffected colon mucosa from patients with mild inflammatory bowel disease

Authors:
- Lili Xu
- Lili Ma
- Jingjing Lian
- Jiayin Yang
- Shiyao Chen
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Affiliations: Division of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
Published online on: February 5, 2016 https://doi.org/10.3892/mmr.2016.4880
Pages: 2729-2735

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Abstract

An endoscopic examination is currently the most reliable method for monitoring disease activity in patients with inflammatory bowel disease (IBD). However, endoscopic evaluations are unable to detect mucosal inflammation at the earliest stages. The present study aimed to evaluate the molecular profiles of inflamed and unaffected colon mucosa from patients with mild Crohn's disease (CD) and ulcerative colitis (UC), in order to identify a more sensitive method for monitoring mucosal impairment. Patients were recruited and colon biopsies from the inflamed and the normal‑appearing mucosa of patients with mild IBD were obtained by colonoscopy. Gene expression analysis was performed using microarrays, after which Gene Ontology and clustering were performed using bioinformatics. In addition, the levels of inflammatory cytokines were analyzed by reverse transcription‑quantitative polymerase chain reaction. A total of 620 genes in the inflamed and 210 genes in the unaffected colon mucosa with at least a 3‑fold change, as compared with healthy controls, were detected in patients with mild CD, and 339 genes in the inflamed and 483 genes in the unaffected colon mucosa were detected in patients with mild UC. Heat mapping demonstrated a similarity in the gene alteration patterns, and altered transcripts overlapped, between the inflamed and unaffected colon mucosa. Interferon‑γ and interleukin‑17 mRNA levels were comparably elevated in the inflamed and unaffected colon mucosa from patients with IBD. Marked gene expression alterations were detected in the inflamed and unaffected colon mucosa from patients with mild IBD, and these showed marked similarity and overlap between the two groups. The results of the present study suggested that inflammation was not limited to the endoscopic lesions and that gene expression profiling may be considered a sensitive tool for monitoring mucosal inflammation, predicting relapses and optimizing therapeutic strategies for patients with IBD.

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1	Orlando A, Mocciaro F, Renna S, Scimeca D, Rispo A, Lia Scribano M, Testa A, Aratari A, Bossa F, Tambasco R, et al: Early post-operative endoscopic recurrence in Crohn's disease patients: data from an Italian Group for the study of inflammatory bowel disease (IG-IBD) study on a large prospective multicenter cohort. J Crohns Colitis. 8:1217–1221. 2014. View Article : Google Scholar : PubMed/NCBI
2	Pineton de Chambrun GP and Sandborn WJ: IBD in 2011: Advances in IBD management-towards a tailored approach. Nat Rev Gastroenterol Hepatol. 9:70–72. 2012. View Article : Google Scholar : PubMed/NCBI
3	Martin TD, Chan SS and Hart AR: environmental factors in the relapse and recurrence of inflammatory bowel disease: A review of the literature. Dig Dis Sci. 60:1396–1405. 2015. View Article : Google Scholar
4	Spooren CE, Pierik MJ, Zeegers MP, Feskens EJ, Masclee AA and Jonkers DM: Review article: The association of diet with onset and relapse in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 38:1172–1187. 2013. View Article : Google Scholar : PubMed/NCBI
5	Schaffer T and Schoepfer AM: Serum ficolin-2 correlates worse than fecal calprotectin and CRP with endoscopic Crohn's disease activity. J Crohns Colitis. 8:1125–1132. 2014. View Article : Google Scholar : PubMed/NCBI
6	Minar P, Haberman Y, Jurickova I, Wen T, Rothenberg ME, Kim MO, Saeed SA, Baldassano RN, Stephens M, Markowitz J, et al: Utility of neutrophil Fcγ receptor I (CD64) index as a biomarker for mucosal inflammation in pediatric Crohn's disease. Inflamm Bowel Dis. 20:1037–1048. 2014.PubMed/NCBI
7	Däbritz J, Bonkowski E, Chalk C, Trapnell BC, Langhorst J, Denson LA and Foell D: Granulocyte macrophage colony-stimulating factor auto-antibodies and disease relapse in inflammatory bowel disease. Am J Gastroenterol. 108:1901–1910. 2013. View Article : Google Scholar : PubMed/NCBI
8	Naismith GD, Smith LA, Barry SJ, Munro JI, Laird S, Rankin K, Morris AJ, Winter JW and Gaya DR: A prospective evaluation of the predictive value of faecal calprotectin in quiescent Crohn's disease. J Crohns Colitis. 8:1022–1029. 2014. View Article : Google Scholar : PubMed/NCBI
9	Foell D, Wittkowski H and Roth J: Monitoring disease activity by stool analyses: From occult blood to molecular markers of intestinal inflammation and damage. Gut. 58:859–868. 2009. View Article : Google Scholar : PubMed/NCBI
10	Masclee GM, Penders J, Jonkers DM, Wolffs PF and Pierik MJ: Is clostridium difficile associated with relapse of inflammatory bowel disease? Results from a retrospective and prospective cohort study in the Netherlands. Inflamm Bowel Dis. 19:2125–2131. 2013. View Article : Google Scholar : PubMed/NCBI
11	Sorrentino D, Nash P, Viladomiu M, Hontecillas R and Bassaganya-Riera J: Stopping anti-TNF agents in patients with Crohn's disease in remission: Is it a feasible long-term strategy? Inflamm Bowel Dis. 20:7570–766. 2014.
12	Dai C, Liu WX, Jiang M and Sun MJ: Mucosal healing did not predict sustained clinical remission in patients with ibd after discontinuation of one-year infliximab therapy. PLoS One. 9:e1107972014. View Article : Google Scholar : PubMed/NCBI
13	Kennedy NA, Kalla R, Warner B, Gambles CJ, Musy R, Reynolds S, Dattani R, Nayee H, Felwick R, Harris R, et al: Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: Relapse and recapture rates, with predictive factors in 237 patients. Aliment Pharmacol Ther. 40:1313–1323. 2014. View Article : Google Scholar : PubMed/NCBI
14	Regueiro M, Kip KE, Baidoo L, Swoger JM and Schraut W: Postoperative therapy with infliximab prevents long-term Crohn's disease recurrence. Clin Gastroenterol Hepatol. 12:1494–1502. 2014. View Article : Google Scholar : PubMed/NCBI
15	Farkas K, Lakatos PL, Nagy F, Szepes Z, Miheller P, Papp M, Palatka K, Bálint A, Bor R, Wittmann T and Molnár T: Predictors of relapse in patients with ulcerative colitis in remission after one-year of infliximab therapy. Scand J Gastroenterol. 48:1394–1398. 2013. View Article : Google Scholar : PubMed/NCBI
16	Keyashian K: Does endoscopic assessment of mucosal healing affect IBD management? Dig Dis Sci. 59:2351–2353. 2014. View Article : Google Scholar : PubMed/NCBI
17	Mańkowska-Wierzbicka D, Swora-Cwynar E, Poniedziałek B, Adamski Z, Dobrowolska A and Karczewski J: Usefulness of selected laboratory markers in ulcerative colitis. Eur Cytokine Netw. Oct 13–2015.Epub ahead of print.
18	Monteleone G, Di Sabatino A, Ardizzone S, Pallone F, Usiskin K, Zhan X, Rossiter G and Neurath MF: Impact of patient characteristics on the clinical efficacy of mongersen (GED-0301), an oral Smad7 antisense oligonucleotide, in active Crohn's disease. Aliment Pharmacol Ther. Jan 13–2016.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar
20	Neurath MF: Cytokines in inflammatory bowel disease. Nat Rev Immunol. 14:329–342. 2014. View Article : Google Scholar : PubMed/NCBI
21	Hundorfean G, Neurath MF and Mudter J: Functional relevance of T helper 17 (Th17) cells and the IL-17 cytokine family in inflammatory bowel disease. Inflamm Bowel Dis. 18:180–186. 2012. View Article : Google Scholar
22	Aine B, Grainne L and Kate K: Transcriptional profiling of the colonic mucosa and epithelial cells of patients with acutely active ulcerative colitis. Inflamm Bowel Dis. (Suppl 1): S10–S11. 2014. View Article : Google Scholar
23	Yanai H, Ben-Shachar S, Baram L, Elad H, Gitstein G, Brazowski E, Tulchinsky H, Pasmanik-Chor M and Dotan I: Gene expression alterations in ulcerative colitis patients after restorative proctocolectomy extend to the small bowel proximal to the pouch. Gut. 64:756–764. 2015. View Article : Google Scholar
24	Abraham C and Medzhitov R: Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterology. 140:1729–1737. 2011. View Article : Google Scholar : PubMed/NCBI
25	MacDonald TT, Biancheri P, Sarra M and Monteleone G: What's the next best cytokine target in IBD? Inflamm Bowel Dis. 18:2180–2189. 2012. View Article : Google Scholar : PubMed/NCBI
26	Cader MZ and Kaser A: Recent advances in inflammatory bowel disease: Mucosal immune cells in intestinal inflammation. Gut. 62:1653–1664. 2013. View Article : Google Scholar : PubMed/NCBI
27	Henderson P, van Limbergen JE, Schwarze J and Wilson DC: Function of the intestinal epithelium and its dysregulation in inflammatory bowel disease. Inflamm Bowel Dis. 17:382–395. 2011. View Article : Google Scholar
28	Nguyen GC, Patel H and Chong RY: Increased prevalence of and associated mortality with methicillin-resistant Staphylococcus aureus among hospitalized IBD patients. Am J Gastroenterol. 105:371–377. 2010. View Article : Google Scholar
29	Bryant RV, Winer S, Travis SP and Riddell RH: Systematic review: Histological remission in inflammatory bowel disease. Is 'complete' remission the new treatment paradigm? An IOIBD initiative. J Crohns Colitis. 8:1582–1597. 2014. View Article : Google Scholar : PubMed/NCBI