title: Neurotrophin Receptor-Interacting Melanoma Antigen-Encoding Gene Homolog is Associated with Malignant Phenotype of Gastric Cancer.
abstract: BACKGROUND
  Identification of novel molecules implicated in the malignancy of gastric cancer (GC) is key to the development of personalized treatments and the improvement of patient outcome. Neurotrophin receptor-interacting melanoma antigen-encoding protein (NRAGE) regulates apoptosis and metastasis via interactions with various genes. This study aimed to evaluate the function and clinical significance of NRAGE in GC.
  
  
  METHODS
  The expression of NRAGE and its putative interacting genes apoptosis antagonizing transcription factor (AATF), p75 neurotrophin receptor (p75NTR), and proliferating cell nuclear antigen (PCNA) were determined in GC cell lines using reverse transcription-polymerase chain reaction (RT-PCR). The effect of NRAGE knockdown by small interfering RNA (siRNA) on GC cell behavior also was evaluated. In addition, NRAGE expression was determined in 179 pairs of resected gastric tissues.
  
  
  RESULTS
  Expression of NRAGE mRNA positively correlated with that of AATF, and NRAGE knockdown significantly decreased the proliferation, migration, and invasion of GC cells. The mean level of NRAGE mRNA expression was significantly higher in GC tissues than in corresponding adjacent normal tissues. The expression patterns of NRAGE mRNA and protein were closely correlated. A stepwise elevation in NRAGE mRNA expression in GC tissues was observed with increasing Union for International Cancer Control (UICC) stage. High NRAGE expression in GCs was associated with shortened recurrence-free survival and identified as an independent prognostic factor (hazard ratio, 1.83; 95 % CI, 1.12-3.02, p = 0.017).
  
  
  CONCLUSIONS
  The results indicate that NRAGE represents a putative oncogene associated with a malignant phenotype of GC. In GC, NRAGE may serve as a predictive biomarker and a target of molecular therapy.
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan. m-kanda@med.nagoya-u.ac.jp.
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authors.lastname: Kanda
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
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authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Ryoji
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Satoshi
authors.initials: S
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Naoki
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authors.lastname: Iwata
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Chie
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
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authors.initials: H
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masahiko
authors.initials: M
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Michitaka
authors.initials: M
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authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
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