title: Gene expression signature and the prediction of ulcerative colitis-associated colorectal cancer by DNA microarray.
abstract: OBJECTIVE
  Ulcerative colitis (UC) is associated with a high risk of colorectal cancer. To identify genes that could predict the development of cancer in UC, we conducted a DNA microarray analysis using nonneoplastic rectal mucosa of UC patients.
  
  
  METHODS
  Gene expression in nonneoplastic mucosa of 53 UC patients were examined. Gene expression profiles were examined using human Genome U133 Plus 2.0 gene chip array (Affymetrix). Among 53 UC patients, 10 had UC-associated cancer (UC-Ca group) whereas 43 did not (UC-NonCa group).
  
  
  RESULTS
  By comparing gene expression profiles of nonneoplastic rectal mucosae between the UC-Ca and UC-NonCa groups, we could identify 40 genes that were differentially expressed between two groups. The list of discriminating genes included low-density lipoprotein receptor-related protein (LRP5 and LRP6). Previous studies suggested that LRP5 and LRP6 expression promotes cancer cell proliferation and tumorigenesis and are considered as candidate oncogenes. In the present study, both LRP5 and LRP6 showed significantly higher expression in the UC-Ca group, which suggests the importance of these genes in the development of UC-associated colorectal cancers. With the 40 selected discriminating genes, we did class prediction of the development of colorectal neoplasms in UC patients. Using the k-nearest neighbor method and the support vector machine, we could predict the development of UC-associated neoplasms with an accuracy of 86.8% and 98.1%, respectively.
  
  
  CONCLUSIONS
  These findings have important implications for the early detection of malignant lesions in UC and may provide directions for future research into the molecular mechanisms of UC-associated cancer.
authors.affiliation: Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. toshwatanabe@yahoo.co.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobunai
authors.forename: Etsuko
authors.initials: E
authors.lastname: Toda
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Yoshihiro
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authors.lastname: Kazama
authors.forename: Junichiro
authors.initials: J
authors.lastname: Tanaka
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hata
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kojima
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Konishi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Okayama
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Toshinori
authors.initials: T
authors.lastname: Oka
authors.forename: Shin
authors.initials: S
authors.lastname: Sasaki
authors.forename: Yohichi
authors.initials: Y
authors.lastname: Ajioka
authors.forename: Tetsuichiro
authors.initials: T
authors.lastname: Muto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D003093:Colitis, Ulcerative / Q000150:complications*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D012306:Risk; D016896:Treatment Outcome