title: Prediction of liver metastasis after colorectal cancer using reverse transcription-polymerase chain reaction analysis of 10 genes.
abstract: OBJECTIVE
  Liver metastasis is one of the major types of recurrence after surgery for colorectal cancer. Traditional methods of predicting liver metastasis are limited in their accuracy, suggesting the need to develop new predictors. We developed a 10-gene signature that is closely associated with the development of liver metastasis after colorectal cancer.
  
  
  METHODS
  We examined a total of 189 frozen specimens of primary colorectal cancers using both microarray and quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Initially, we studied gene expression in colorectal cancer tissue from 160 randomly selected patients who had undergone surgical resection of colorectal cancer and evaluated the association between the level of gene expression and the occurrence of liver metastasis. We developed a gene-expression model for the prediction of liver metastasis based on the RT-PCR findings. We then used specimens from 29 other patients for validation.
  
  
  RESULTS
  The expression of 14 genes was correlated with liver metastasis according to both microarray and RT-PCR analysis. We constructed an accurate predictive model based on the results for 10 of these genes, which included epiregulin (EREG), amphiregulin (AREG), cyclooxygenase 2 (COX-2) and lymphocyte-specific protein tyrosine kinase (LCK). The 10-gene signature was an independent predictor of liver metastasis. The model was validated in the independent set of 29 patients. The predictive accuracy of the model in a test set of patients was 86.2%.
  
  
  CONCLUSIONS
  The 10-gene signature identified in this study is closely associated with the occurrence of liver metastasis in colorectal cancer patients.
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: Yoko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Konishi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
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: Kiyoshi
authors.initials: K
authors.lastname: Eshima
authors.forename: Tetsuichiro
authors.initials: T
authors.lastname: Muto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000556:secondary*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult