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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2017

01-03-2017 | Translational Research and Biomarkers

Clinical Significance of Histone Demethylase NO66 in Invasive Colorectal Cancer

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

Published in: Annals of Surgical Oncology | Issue 3/2017

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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.
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Metadata
Title
Clinical Significance of Histone Demethylase NO66 in Invasive Colorectal Cancer
Authors
Yujiro Nishizawa, MD
Naohiro Nishida, MD, PhD
Masamitsu Konno, PhD
Koichi Kawamoto, MD, PhD
Ayumu Asai, PhD
Jun Koseki, PhD
Hidekazu Takahashi, MD, PhD
Naotsugu Haraguchi, MD, PhD
Junichi Nishimura, MD, PhD
Taishi Hata, MD, PhD
Chu Matsuda, MD, PhD
Tsunekazu Mizushima, MD, PhD
Taroh Satoh, MD, PhD
Yuichiro Doki, MD, PhD
Masaki Mori, MD, PhD, FACS
Hideshi Ishii, MD, PhD
Publication date
01-03-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 3/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5395-9

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