title: Comprehensive molecular exploration identified promoter DNA methylation of the CRBP1 gene as a determinant of radiation sensitivity in rectal cancer.
abstract: BACKGROUND
  Neoadjuvant chemoradiotherapy (NCRT) for advanced rectal cancer (RC) is a well-evidenced therapy; however, some RC patients have no therapeutic response. Patient selection for NCRT so that non-responsive patients are excluded has been subjective. To date, no molecular markers indicating radiation sensitivity have been reported.
  
  
  METHODS
  We irradiated six colorectal cancer (CRC) cell lines and identified HCT116 cells as radiation-sensitive and HCT15 and DLD-1 cells as radiation resistant. Using a microarray, we selected candidate radiation sensitivity marker genes by choosing genes whose expression was consistent with a radiation-resistant or sensitive cell phenotype.
  
  
  RESULTS
  Among candidate genes, cellular retinol binding protein 1 (CRBP1) was of particular interest because it was not only induced in HCT116 cells by tentative 10 Gy radiation treatments, but also its expression was increased in HCT116-derived radiation-resistant cells vs parental cells. Forced expression of CRBP1 decreased the viability of both HCT15 and DLD-1 cells in response to radiation therapy. We also confirmed that CRBP1 was epigenetically silenced by hypermethylation of its promoter DNA, and that the quantitative methylation value of CRBP1 significantly correlated with histological response in RC patients with NCRT (P=0.031).
  
  
  CONCLUSIONS
  Our study identified CRBP1 as a radiation-sensitive predictor in RC.
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato, 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yokoi
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato, 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato, 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ishii
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato, 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato, 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nishizawa
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato, 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tsutsui
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato, 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Miura
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato, 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Katoh
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato, 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamanashi
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato, 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Naito
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato, 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato, 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kitasato, 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D049109:Cell Proliferation; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D054840:Retinol-Binding Proteins, Cellular / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D054840:Retinol-Binding Proteins, Cellular