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Clinical Significance of Histone Demethylase NO66 in Invasive Colorectal Cancer

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
Translational Research and Biomarkers
Volume 24, Issue 3 / March , 2017

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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