Overexpression of mitochondrial GTPase MFN2 represents a negative prognostic marker in human gastric cancer and its inhibition exerts anti-cancer effects

Chia Lang Fang, Ding Ping Sun, Han Kun Chen, Chih Chan Lin, Shih Ting Hung, Yih Huei Uen, Kai Yuan Lin

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1153-1161
Number of pages9
JournalJournal of Cancer
Volume8
Issue number7
DOIs
Publication statusPublished - Apr 9 2017

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GTP Phosphohydrolases
Stomach Neoplasms
Disease-Free Survival
Neoplasms
Survival Rate
Cell Proliferation
Small Interfering RNA
Blood Vessels
Stomach
Proteins
Immunohistochemistry
Regression Analysis
Technology
Survival
Therapeutics

Keywords

  • Gastric cancer
  • MFN2
  • Prognosis

ASJC Scopus subject areas

  • Oncology

Cite this

Overexpression of mitochondrial GTPase MFN2 represents a negative prognostic marker in human gastric cancer and its inhibition exerts anti-cancer effects. / Fang, Chia Lang; Sun, Ding Ping; Chen, Han Kun; Lin, Chih Chan; Hung, Shih Ting; Uen, Yih Huei; Lin, Kai Yuan.

In: Journal of Cancer, Vol. 8, No. 7, 09.04.2017, p. 1153-1161.

Research output: Contribution to journalArticle

Fang, Chia Lang ; Sun, Ding Ping ; Chen, Han Kun ; Lin, Chih Chan ; Hung, Shih Ting ; Uen, Yih Huei ; Lin, Kai Yuan. / Overexpression of mitochondrial GTPase MFN2 represents a negative prognostic marker in human gastric cancer and its inhibition exerts anti-cancer effects. In: Journal of Cancer. 2017 ; Vol. 8, No. 7. pp. 1153-1161.
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AU - Hung, Shih Ting

AU - Uen, Yih Huei

AU - Lin, Kai Yuan

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N2 - 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.

AB - 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.

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