Clinical Significance of Histone Demethylase NO66 in Invasive Colorectal Cancer

Yujiro Nishizawa, Naohiro Nishida, Masamitsu Konno, Koichi Kawamoto, Ayumu Asai, Jun Koseki, Hidekazu Takahashi, Naotsugu Haraguchi, Junichi Nishimura, Taishi Hata, Chu Matsuda, Tsunekazu Mizushima, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii

Research output: Contribution to journalArticle

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Abstract

Background: Targeting epigenetic regulators is a promising therapeutic strategy against cancer. However, because of the broad spectrum of targets, selective inhibition of cancer-associated genes remains a major challenge. To address this issue, we focused on the oncogene-regulated histone demethylase, nucleolar protein 66 (NO66 [C14orf169/MAPJD]), which is known to work coordinately with the well-characterized oncogene, c-MYC. Methods: To investigate expression patterns and clinical significance of NO66 in colorectal cancer (CRC), we performed immunohistochemical staining in 114 CRC cases. We performed functional analysis of NO66 to evaluate its contribution to proliferation and migration ability in CRC cells in vitro. Results: NO66 was selectively expressed in CRC tissues. Furthermore, high expression levels of NO66 were associated with cancer metastatic potential, including lymphatic duct invasion (p = 0.047), venous invasion (p = 0.033), and lymph node metastasis (p = 0.015). Multivariate analysis indicated that NO66 was an independent prognostic factor for overall survival. In vitro assays revealed that NO66 expression is closely associated with malignant potential, including proliferation, migration and anti-apoptotic activity. Conclusions: NO66 is an independent prognostic factor in CRC. The cancer-selective expression patterns and its involvement in metastatic phenotypes suggest that NO66 is not only a crucial biomarker but is also a promising therapeutic target in CRC.

Original languageEnglish
Pages (from-to)841-849
Number of pages9
JournalAnnals of Surgical Oncology
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 1 2017

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Histone Demethylases
Colorectal Neoplasms
Oncogenes
Neoplasms
Neoplasm Genes
Nuclear Proteins
Epigenomics
Multivariate Analysis
Biomarkers
Lymph Nodes
Staining and Labeling
Neoplasm Metastasis
Phenotype
Therapeutics

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Nishizawa, Y., Nishida, N., Konno, M., Kawamoto, K., Asai, A., Koseki, J., ... Ishii, H. (2017). Clinical Significance of Histone Demethylase NO66 in Invasive Colorectal Cancer. Annals of Surgical Oncology, 24(3), 841-849. https://doi.org/10.1245/s10434-016-5395-9

Clinical Significance of Histone Demethylase NO66 in Invasive Colorectal Cancer. / Nishizawa, Yujiro; Nishida, Naohiro; Konno, Masamitsu; Kawamoto, Koichi; Asai, Ayumu; Koseki, Jun; Takahashi, Hidekazu; Haraguchi, Naotsugu; Nishimura, Junichi; Hata, Taishi; Matsuda, Chu; Mizushima, Tsunekazu; Satoh, Taroh; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi.

In: Annals of Surgical Oncology, Vol. 24, No. 3, 01.03.2017, p. 841-849.

Research output: Contribution to journalArticle

Nishizawa, Y, Nishida, N, Konno, M, Kawamoto, K, Asai, A, Koseki, J, Takahashi, H, Haraguchi, N, Nishimura, J, Hata, T, Matsuda, C, Mizushima, T, Satoh, T, Doki, Y, Mori, M & Ishii, H 2017, 'Clinical Significance of Histone Demethylase NO66 in Invasive Colorectal Cancer', Annals of Surgical Oncology, vol. 24, no. 3, pp. 841-849. https://doi.org/10.1245/s10434-016-5395-9
Nishizawa Y, Nishida N, Konno M, Kawamoto K, Asai A, Koseki J et al. Clinical Significance of Histone Demethylase NO66 in Invasive Colorectal Cancer. Annals of Surgical Oncology. 2017 Mar 1;24(3):841-849. https://doi.org/10.1245/s10434-016-5395-9
Nishizawa, Yujiro ; Nishida, Naohiro ; Konno, Masamitsu ; Kawamoto, Koichi ; Asai, Ayumu ; Koseki, Jun ; Takahashi, Hidekazu ; Haraguchi, Naotsugu ; Nishimura, Junichi ; Hata, Taishi ; Matsuda, Chu ; Mizushima, Tsunekazu ; Satoh, Taroh ; Doki, Yuichiro ; Mori, Masaki ; Ishii, Hideshi. / Clinical Significance of Histone Demethylase NO66 in Invasive Colorectal Cancer. In: Annals of Surgical Oncology. 2017 ; Vol. 24, No. 3. pp. 841-849.
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AU - Konno, Masamitsu

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AU - Asai, Ayumu

AU - Koseki, Jun

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AU - Matsuda, Chu

AU - Mizushima, Tsunekazu

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