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Article

Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer

  • Authors:
    • Shinichiro Saito
    • Hideyuki Ishiguro
    • Masahiro Kimura
    • Ryo Ogawa
    • Hirotaka Miyai
    • Tatsuya Tanaka
    • Koji Mizoguchi
    • Hiromitsu Takeyama
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Honshu 467-8601, Japan
  • Pages: 344-348
    |
    Published online on: July 27, 2016
       https://doi.org/10.3892/br.2016.723
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Abstract

Recent studies have shown constitutive activation of the Notch signaling pathway in various types of malignancies. However, it remains unclear whether this signaling pathway is activated in gastric cancer. In the present study, the aim was to investigate the role of Notch signaling in gastric cancer by investigating the subcellular localization of Notch-associated proteins in tissue samples from gastric cancer patients. Samples were obtained from 115 gastric cancer patients who had undergone surgery at the Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science without pre-operative chemotherapy or radiation. Subsequently the correlation between translocation of NOTCH1 intracellular cytoplasmic domain (NICD) into the nucleus (as measured by immunostaining) and survival in gastric cancer patients after surgery was investigated. The results were analyzed in reference to the patients' clinicopathological characteristics and the effects of these results on patient prognosis were determined. Significant correlations were observed between NICD nuclear localization and clinicopathological characteristics, such as tumor status (T factor), lymph node status (N factor), pathological stage and differentiation status. No significant correlations were observed between NICD nuclear localization and age, gender, tumor location, vein invasion or lymphatic invasion. Patients with >30% of cancer cell nuclei positively stained for NICD (as revealed by immunostaining) were associated with a significantly shorter survival following surgery than patients with <30% NICD-positive cancer cell nuclei (log-rank test, P=0.0194). Univariate analysis revealed that among the clinicopathological factors examined, T factor [risk rate (RR)=10.870; P=0.0016], N factor (RR=41.667; P=0.0003), lymphatic invasion (RR=13.158; P=0.0125), vein invasion (RR=25.000; P= 0.0019) and translocation of NICD to the nucleus (RR=3.937; P=0.0312) were all identified to be statistically significant prognostic factors. However, multivariate analysis revealed that translocation of NICD to the nucleus was not independently associated with an unfavourable prognosis in patients with gastric cancer. The present results suggest that NOTCH1 acts as an oncogene in gastric cancer. It is hypothesized that translocation of NICD into the nucleus may be used as a therapeutic target in gastric cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Saito S, Ishiguro H, Kimura M, Ogawa R, Miyai H, Tanaka T, Mizoguchi K and Takeyama H: Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer. Biomed Rep 5: 344-348, 2016.
APA
Saito, S., Ishiguro, H., Kimura, M., Ogawa, R., Miyai, H., Tanaka, T. ... Takeyama, H. (2016). Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer. Biomedical Reports, 5, 344-348. https://doi.org/10.3892/br.2016.723
MLA
Saito, S., Ishiguro, H., Kimura, M., Ogawa, R., Miyai, H., Tanaka, T., Mizoguchi, K., Takeyama, H."Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer". Biomedical Reports 5.3 (2016): 344-348.
Chicago
Saito, S., Ishiguro, H., Kimura, M., Ogawa, R., Miyai, H., Tanaka, T., Mizoguchi, K., Takeyama, H."Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer". Biomedical Reports 5, no. 3 (2016): 344-348. https://doi.org/10.3892/br.2016.723
Copy and paste a formatted citation
x
Spandidos Publications style
Saito S, Ishiguro H, Kimura M, Ogawa R, Miyai H, Tanaka T, Mizoguchi K and Takeyama H: Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer. Biomed Rep 5: 344-348, 2016.
APA
Saito, S., Ishiguro, H., Kimura, M., Ogawa, R., Miyai, H., Tanaka, T. ... Takeyama, H. (2016). Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer. Biomedical Reports, 5, 344-348. https://doi.org/10.3892/br.2016.723
MLA
Saito, S., Ishiguro, H., Kimura, M., Ogawa, R., Miyai, H., Tanaka, T., Mizoguchi, K., Takeyama, H."Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer". Biomedical Reports 5.3 (2016): 344-348.
Chicago
Saito, S., Ishiguro, H., Kimura, M., Ogawa, R., Miyai, H., Tanaka, T., Mizoguchi, K., Takeyama, H."Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer". Biomedical Reports 5, no. 3 (2016): 344-348. https://doi.org/10.3892/br.2016.723
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