Persistence of gene expression changes in noninflamed and inflamed colonic mucosa in ulcerative colitis and their presence in colonic carcinoma

Abstract

Aim: A few studies have applied genomic-wide gene expression analysis in inflamed colon tissue sample in ulcerative colitis (UC). We reported the first study of non-inflamed mucosal gene expression in UC and explored its clinical implication.

Methods: Non-inflamed mucosa was obtained from 6 UC patients who received total colectomy. The gene expression of UC in noninflamed mucosa was monitored with a microarray. For a selected gene, RT-PCR was performed to verify array results and to further examine expression pattern in inflamed mucosa of UC, colorectal cancer tissue and normal mucosa using additional matched pairs.

Results: Two genes showing 2.5-fold decreased expression with significance set at in UC samples were homeo box a4 (HOXa4) and mads box transcription enhancer factor 2, polypeptide B (MEF2b). RT-PCR showed that MEF2b expression in non-inflamed mucosa was significantly downregulated, whereas the expression of MEF2b increased in accordance with the severity of mucosal inflammation. HOXa4 expression both in inflamed and non-inflamed mucosa in UC was consistently downregulated, and the downregulation of HOXa4 was also found in colorectal carcinoma.

Conclusion: It is suggested that the MEF2b expression in UC which increase in accordance with inflammation may be induced by the inflammatory mediator. In contrast the downregulation of HOXa4 may be partly involved in the pathogenesis of disease including UC and UC-related carcinogenesis.

Figure 1

Comparison of expression of genes in non-inflamed mucosa of ulcerative colitis (UC) and normal control mucosa. The upper and lower boundaries represent a 2- and 0.5-fold difference in the mean of the expression of each gene between noninflamed UC mucosa and control, respectively. Axis scales are logarithmic.

Figure 2

RT-PCR analysis of HOXa4 gene expression in normal colonic mucosa and UC mucosa (inflamed, non-inflamed). A: Showed RT-PCR was performed on four paired inflamed mucosa (I) and non-inflamed mucosa (NI) samples in UC as well as six normal control mucosa (N1-N6) G3PDH was used as a control for cDNA synthesis; B: Semiquantification of HOXa4 gene expression (HOXa4/G3PDH) was performed in six paired UC mucosa and six normal control mucosa using NIH image software.

Figure 3

RT-PCR analysis of MEF2b gene expression in normal colonic mucosa and UC mucosa (inflamed, non-inflamed). A: Analysis was performed on five normal control mucosa (N1-N5) and three non-inflamed UC mucosa (NI) was performed on four paired inflamed mucosa (I) and non-inflamed mucosa (NI); B: Analysis was performed on four paired inflamed mucosa (I) and non-inflamed mucosa (NI). G3PDH was used as a control for cDNA synthesis; C and D: Semiquantification of MEF2b gene expression (MEF2b/G3PDH) was performed in six paired UC mucosa and six normal control mucosa using NIH image software.

Figure 4

(A and B) RT-PCR analysis of HOXa4 and MEF2b gene expression in eight paired colon cancer (C) and normal colonic mucosa (N). G3PDH was used as a control for cDNA synthesis. (C and D) Semiquantification of HOXa4 and MEF2b gene expression (HOXa4, MEF2b/G3PDH) was performed in eight paired colon cancer and normal colonic mucosa using NIH image software.