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


CONCLUSIONS
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.
Toiyama
Yuji
Y
Second Department of Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Mizoguchi
Akira
A
Kimura
Kazushi
K
Araki
Toshimitsu
T
Yoshiyama
Shigeyuki
S
Sakaguchi
Kouhei
K
Miki
Chikao
C
Kusunoki
Masato
M
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000378:metabolism*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008875:Middle Aged