Open AccessClinical significance of UNC5B expression in colorectal cancer
Author(s) -
Satoshi Okazaki,
Toshiaki Ishikawa,
Satoru Iida,
Megumi Ishiguro,
Hirotoshi Kobayashi,
Tetsuro Higuchi,
Masayuki Enomoto,
Kaoru Mogushi,
Hiroshi Mizushima,
Hiroshi Tanaka,
Hiroyuki Uetake,
Kenichi Sugihara
Publication year - 2011
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2011.1201
Subject(s) - dna methylation , oncogene , cancer research , colorectal cancer , cancer , biomarker , methylation , biology , gene expression , molecular medicine , cell cycle , gene , oncology , medicine , genetics
The purpose of this study was to find a methylation-related gene that couldbecome a biomarker or therapeutic target in colorectal carcinoma (CRC). We screenedcandidate genes suspected to be silenced by DNA methylation using cDNA microarrayanalysis. To investigate the clinical significance of one candidate gene (UNC5B),we analyzed the correlation between mRNA expression and clinicopathological featuresusing clinical tissue samples. Moreover, methylation specific PCR analysis wasperformed to reveal whether the promoter region was methylated in CRC cell lines.We found 75 candidate genes that were potentially suppressed by DNA methylationin CRC. We focused on UNC5B, a possible tumor suppressor gene and regulator ofapoptosis known to be inactivated in CRC. The mRNA expression analysis using tissuesamples revealed that UNC5B mRNA was down-expressed in about 20% of CRC patients,and the patients with low-UNC5B-expression tumors showed a significantly higherrecurrence rate after curative surgery. According to the univariate and multivariateanalysis, low UNC5B expression was an independent risk factor for postoperativerecurrence in stage I, II and III CRC patients. Furthermore, patients with lowexpression of UNC5B in tumors had significantly poorer prognosis than those withhigh expression of UNC5B. Although UNC5B mRNA expression was restored by the demethylationtreatment in CRC cell lines, the promoter region of UNC5B was not methylated.UNC5B is a potential biomarker for the selection of patients with high risk ofpostoperative recurrence and worse prognosis in CRC.