title: Clinical significance of UNC5B expression in colorectal cancer.
abstract: The purpose of this study was to find a methylation-related gene that could             become a biomarker or therapeutic target in colorectal carcinoma (CRC). We screened             candidate genes suspected to be silenced by DNA methylation using cDNA microarray             analysis. To investigate the clinical significance of one candidate gene (UNC5B),             we analyzed the correlation between mRNA expression and clinicopathological features             using clinical tissue samples. Moreover, methylation specific PCR analysis was             performed to reveal whether the promoter region was methylated in CRC cell lines.             We found 75 candidate genes that were potentially suppressed by DNA methylation             in CRC. We focused on UNC5B, a possible tumor suppressor gene and regulator of             apoptosis known to be inactivated in CRC. The mRNA expression analysis using tissue             samples revealed that UNC5B mRNA was down-expressed in about 20% of CRC patients,             and the patients with low-UNC5B-expression tumors showed a significantly higher             recurrence rate after curative surgery. According to the univariate and multivariate             analysis, low UNC5B expression was an independent risk factor for postoperative             recurrence in stage I, II and III CRC patients. Furthermore, patients with low             expression of UNC5B in tumors had significantly poorer prognosis than those with             high expression of UNC5B. Although UNC5B mRNA expression was restored by the demethylation             treatment 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 of             postoperative recurrence and worse prognosis in CRC.
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan. sokazaki@musashino.jrc.or.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okazaki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Iida
authors.forename: Megumi
authors.initials: M
authors.lastname: Ishiguro
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Higuchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Enomoto
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizushima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uetake
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000075386:Netrin Receptors; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D000075386:Netrin Receptors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C532445:UNC5B protein, human