Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world [1–3]. Approximately 437,000 people are diagnosed with HCC each year worldwide, of which approximately 50% occur in China.

A total of 107 HCC specimens were collected for tissue microarray analysis and immunohistochemistry (IHC) analysis. The relationship between MFN2 expression and clinical features of patients with HCC was analyzed.

The expression level of MFN2 in HCC tissues was 0.92 ± 0.78, significantly lower than that of matched paracancerous liver tissues (1.25 ± 0.75). Patients with low expression of MFN2 had significantly higher rates of cirrhosis than those with high expression of MFN2 (P = 0.049).

Kaplan-Meier survival analysis showed that HCC patients with low expression of MFN2 had a worse prognosis in overall survival than HCC patients with high expression of MFN2 (P = 0.027). Patients with high expression of MFN2 had a better prognosis in disease-free survival compared with HCC patients with low expression of MFN2 (P = 0.047).

Vascular invasion and MFN2 expression were shown to be prognostic variables for overall survival in patients with HCC. Multivariate analysis showed that vascular invasion (P < 0.001) and MFN2 expression (P = 0.045) were independent prognostic factors for overall survival.

Vascular invasion (P < 0.001) and MFN2 expression (P = 0.042) were independent risk factors associated with disease-free survival. The data revealed that MFN2 expression was decreased in HCC samples.

A therapeutic target for the disease

High MFN2 expression was correlated with longer survival times in patients with HCC and served as an independent factor for better outcomes. The study, therefore, provides a promising biomarker for the prognostic prediction of HCC and a potential therapeutic target for the disease.

In addition, studies also showed that exogenous MFN2 can inhibit the proliferation of gastric cancer cells and induce apoptosis in vitro by promoting the flow of calcium ions from the endoplasmic reticulum to mitochondria, thereby disrupting the mitochondrial calcium ion homeostasis.

However, the role of MFN2 in HCC is still unclear. This study demonstrated that low expression of MFN2 is closely related to the poor prognosis of patients with HCC, and the specific molecular mechanism warrants further study.

In addition, since all patients enrolled in our study were HBV-related HCC patients. Therefore, we conclude that MFN2 can be used as a prognostic biomarker for HBV-related HCC. However, for HCV or non-viral related HCC, whether MFN2 can be used as a biomarker for prognosis still needs further study.

Since in China, most HCC is caused by chronic HBV infection. Therefore, exploring the expression level and significance of MFN2 in HCC caused by other etiologies still needs a multi-center clinical study to confirm.