J Cancer 2017; 8(7):1153-1161. doi:10.7150/jca.17986

Research Paper

Overexpression of Mitochondrial GTPase MFN2 Represents a Negative Prognostic Marker in Human Gastric Cancer and Its Inhibition Exerts Anti-Cancer Effects

Chia-Lang Fang1, 2, Ding-Ping Sun3, 4, Han-Kun Chen3, Chih-Chan Lin5, Shih-Ting Hung5, Yih-Huei Uen6✉, Kai-Yuan Lin5, 7✉

1. Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;
2. Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;
3. Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan;
4. Department of Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan;
5. Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan;
6. The Superintendent's Office, Chi Mei Hospital Chiali, Tainan, Taiwan;
7. Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.

Abstract

Background: As one of the most common malignancies in the world, little is known about the molecular mechanism underlying gastric cancer (GC) and its progression. In this study, we aimed to investigate the clinical impact of the mitochondrial GTPase mitofusin 2 (MFN2) in GC.

Methods: Immunohistochemistry was used to examine the expression levels of MFN2 in gastric tissues obtained from 141 patients with GC. The correlations between MFN2 protein level and clinicopathologic parameters, as well as the significance of MFN2 protein level for overall and disease-free survival were assessed. siRNA technology was used to study the effect of MFN2 knockdown on cell proliferation and invasion.

Results: The overexpression of MFN2 was positively associated with depth of invasion (P = 0.0430), stage (P = 0.0325) and vascular invasion (P = 0.0077). Patients with high expression levels of MFN2 had a significantly lower overall survival rate and disease-free survival rate compared with those with low expression levels (P = 0.003 and 0.001, respectively). Multivariate Cox regression analysis showed that the overexpression of MFN2 was an independent prognostic marker for inferior overall survival and disease-free survival (P = 0.015 and 0.025, respectively). In addition, studies conducted in GC cells indicated that knockdown of MFN2 suppressed cell proliferation and invasion.

Conclusions: Overexpression of MFN2 can be used as a marker to predict the outcome of patients with GC. Furthermore, targeting MFN2 might provide a new therapeutic modality for the treatment of GC.

Keywords: gastric cancer, MFN2, prognosis.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Fang CL, Sun DP, Chen HK, Lin CC, Hung ST, Uen YH, Lin KY. Overexpression of Mitochondrial GTPase MFN2 Represents a Negative Prognostic Marker in Human Gastric Cancer and Its Inhibition Exerts Anti-Cancer Effects. J Cancer 2017; 8(7):1153-1161. doi:10.7150/jca.17986. Available from http://www.jcancer.org/v08p1153.htm