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Transcriptomic Landscape of Treatment - Naïve Ulcerative Colitis.

Research paper by Hagar H Taman, Christopher G CG Fenton, Inga V IV Hensel, Endre E Anderssen, Jon J Florholmen, Ruth H RH Paulssen

Indexed on: 19 Oct '17Published on: 19 Oct '17Published in: Journal of Crohn's & colitis



Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease that effects the gastrointestinal tract and is considered one of the most prominent and common forms of inflammatory bowel disease (IBD). This study aimed to define and describe the entire transcriptomic landscape in a well-stratified, treatment-naïve UC patient population compared to control patients by using next-generation technology, RNA-Seq.Mucosal biopsies from treatment-naïve UC patients (n=14), and healthy controls (n=16) underwent RNA-Seq. Principal component analysis (PCA), cell deconvolution methods, and diverse statistical methods were applied to obtain and characterize a dataset of significantly differentially expressed genes (DEGs).Analyses revealed 1480 significantly DEGs in treatment-naïve UC when compared to controls. Cell populations of monocytes, T cells, neutrophils, B cells/ lymphoid cells and myeloid cells were increased during inflammation, while the fraction of epithelial cells were reduced in UC which is reflected by the DEGs. Seventy-nine DEGs were identified as IBD susceptibility genes, and 58 DEGs were expressed in a gender-specific manner. MUC5B, REG3A, DEFA5 and IL33 might be considered as CRC risk factors following UC in males. AQP9 together with CLDN2 may have a role regulating tissue specific physiological properties in tight junctions in UC. An additional functional role for AQP9 in the synthesis and/or the function of mucus can be implied.This study reveals new potential players in UC pathogenesis in general and provides evidence for a gender-dependent pathogenesis for UC. These results can be useful for the development of personalised treatment strategies for UC in the future.

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