title: Diversity of clinical implication of B-cell translocation gene 1 expression by histopathologic and anatomic subtypes of gastric cancer.
abstract: BACKGROUND
  Genetic signatures may differ by histopathologic and anatomic subtypes of gastric cancer (GC). B-cell translocation gene 1 (BTG1) was identified as one of genes downregulated in GC tissues from our microarray data.
  
  
  OBJECTIVE
  To evaluate the clinical implications of BTG1 expression in GC and the genetic diversity among GC subtypes.
  
  
  METHODS
  BTG1 mRNA expression was analyzed in GC cell lines and 233 pairs of surgical specimens. The mutational and methylation status of BTG1 in GC cell lines was analyzed, and immunohistochemistry was conducted to determine the distribution of BTG1. The pattern and prognostic significance of BTG1 expression were correlated with the three proposed GC subtypes.
  
  
  RESULTS
  BTG1 mRNA was downregulated in 82 % of GC cell lines and in 88 % of clinical GC tissues. Promoter hypermethylation events or sequence mutations were not detected in GC cell lines. The pattern of BTG1 expression as observed by immunohistochemistry was consistent with that of its mRNA. Downregulation of BTG1 mRNA in GCs was significantly associated with shorter disease-specific and recurrence-free survival. Multivariate analysis of disease-specific survival identified downregulation of BTG1 transcription as an independent prognostic factor. BTG1 mRNA expression was more strongly suppressed in proximal nondiffuse and diffuse GC compared with distal nondiffuse GC, and subgroup analysis revealed that BTG1 downregulation led to adverse prognosis, specifically in patients with proximal nondiffuse and diffuse GC.
  
  
  CONCLUSIONS
  Altered expression of BTG1 is a potential biomarker for carcinogenesis and progression of GC, particularly for proximal nondiffuse and diffuse GC.
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan, m-kanda@med.nagoya-u.ac.jp.
authors.forename: Mitsuro
authors.initials: M
authors.lastname: Kanda
authors.forename: Hisaharu
authors.initials: H
authors.lastname: Oya
authors.forename: Shuji
authors.initials: S
authors.lastname: Nomoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Takami
authors.forename: Dai
authors.initials: D
authors.lastname: Shimizu
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sueoka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.forename: Chie
authors.initials: C
authors.lastname: Tanaka
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamada
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujii
authors.forename: Goro
authors.initials: G
authors.lastname: Nakayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koike
authors.forename: Michitaka
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D014158:Transcription, Genetic; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C074086:BTG1 protein, human