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

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.

CONCLUSION: 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.