title: Predicting ulcerative colitis-associated colorectal cancer using reverse-transcription polymerase chain reaction analysis.
abstract: BACKGROUND
  Widespread genetic alterations are present not only in ulcerative colitis (UC)-associated neoplastic lesions but also in the adjacent normal colonic mucosa. This suggests that genetic changes in nonneoplastic mucosa might be effective markers for predicting the development of UC-associated cancer (UC-Ca). This study aimed to build a predictive model for the development of UC-Ca based on gene expression levels measured by reverse-transcription polymerase chain reaction (RT-PCR) analysis in nonneoplastic rectal mucosa.
  
  
  METHODS
  Fifty-three UC patients were examined, of which 10 had UC-Ca and 43 did not (UC-NonCa). In addition to the 40 genes and transcripts previously shown to be predictive for developing UC-Ca in our microarray studies, 149 new genes, reported to be important in carcinogenesis, were selected for low density array (LDA) analysis. The expression of a total of 189 genes was examined by RT-PCR in nonneoplastic rectal mucosa.
  
  
  RESULTS
  We identified 20 genes showing differential expression in UC-Ca and UC-NonCa patients, including cancer-related genes such as CYP27B1, RUNX3, SAMSN1, EDIL3, NOL3, CXCL9, ITGB2, and LYN. Using these 20 genes, we were able to build a predictive model that distinguished patients with and without UC-Ca with a high accuracy rate of 83% and a negative predictive value of 100%.
  
  
  CONCLUSIONS
  This predictive model suggests that it is possible to identify UC patients at a high risk of developing cancer. These results have important implications for improving the efficacy of surveillance by colonoscopy and suggest directions for future research into the molecular mechanisms of UC-associated cancer.
authors.affiliation: Department of Surgery, Teikyo University School of Medicine, Tokyo, 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: Yoko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ikeuchi
authors.forename: Keiji
authors.initials: K
authors.lastname: Matsuda
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ishihara
authors.forename: Keijiro
authors.initials: K
authors.lastname: Nozawa
authors.forename: Hisae
authors.initials: H
authors.lastname: Iinuma
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Konishi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Eshima
authors.forename: Yohichi
authors.initials: Y
authors.lastname: Ajioka
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tetsuichiro
authors.initials: T
authors.lastname: Muto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000150:complications* / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor