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Annals of Surgical Oncology

, Volume 23, Supplement 4, pp 532–539 | Cite as

Neurotrophin Receptor-Interacting Melanoma Antigen-Encoding Gene Homolog is Associated with Malignant Phenotype of Gastric Cancer

  • Mitsuro Kanda
  • Dai Shimizu
  • Tsutomu Fujii
  • Haruyoshi Tanaka
  • Yuri Tanaka
  • Kazuhiro Ezaka
  • Masahiro Shibata
  • Hideki Takami
  • Ryoji Hashimoto
  • Satoshi Sueoka
  • Naoki Iwata
  • Daisuke Kobayashi
  • Chie Tanaka
  • Suguru Yamada
  • Goro Nakayama
  • Hiroyuki Sugimoto
  • Masahiko Koike
  • Michitaka Fujiwara
  • Yasuhiro Kodera
Translational Research and Biomarkers

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.

Keywords

Gastric Cancer Proliferate Cell Nuclear Antigen Gastric Cancer Cell Gastric Cancer Cell Line Gastric Cancer Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Conflicts of Interest

There are no conflicts of interest.

Supplementary material

10434_2016_5375_MOESM1_ESM.tif (5.9 mb)
(a) Correlative analysis of NRAGE mRNA expression with that of p75NTR and PCNA in GC cell lines. (b) Analysis of NRAGE and AATF mRNA levels in 179 GC tissues. Supplementary material 1 (TIFF 6033 kb)
10434_2016_5375_MOESM2_ESM.doc (36 kb)
Supplementary material 2 (DOC 36 kb)
10434_2016_5375_MOESM3_ESM.doc (48 kb)
Supplementary material 3 (DOC 47 kb)

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Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • Mitsuro Kanda
    • 1
  • Dai Shimizu
    • 1
  • Tsutomu Fujii
    • 1
  • Haruyoshi Tanaka
    • 1
  • Yuri Tanaka
    • 1
  • Kazuhiro Ezaka
    • 1
  • Masahiro Shibata
    • 1
  • Hideki Takami
    • 1
  • Ryoji Hashimoto
    • 1
  • Satoshi Sueoka
    • 1
  • Naoki Iwata
    • 1
  • Daisuke Kobayashi
    • 1
  • Chie Tanaka
    • 1
  • Suguru Yamada
    • 1
  • Goro Nakayama
    • 1
  • Hiroyuki Sugimoto
    • 1
  • Masahiko Koike
    • 1
  • Michitaka Fujiwara
    • 1
  • Yasuhiro Kodera
    • 1
  1. 1.Department of Gastroenterological Surgery (Surgery II)Nagoya University Graduate School of MedicineNagoyaJapan

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