The evaluative value of Sema3C and MFN2 co-expression detected by immunohistochemistry for prognosis in hepatocellular carcinoma patients after hepatectomy
OncoTargets and Therapy
The evaluative value of sema3c and MFn2 co-expression detected by immunohistochemistry for prognosis in hepatocellular carcinoma patients after hepatectomy
Xu Feng 2
Kelei Zhu 1 2
Jinghua liu 2
Jiang chen 2
Jiacheng Tang 0
Yuelong liang 2
renan Jin 2
Xiao liang 2
Xiujun cai 0 2
0 Key l ab of s urgery of Zhejiang Province, sir run run shaw hospital, Zhejiang University , hangzhou, Zhejiang, People's republic of china
1 Department of g eneral s urgery, Yinzhou People's hospital , n ingbo
2 Department of general surgery, sir run run shaw hospital, Zhejiang University , hangzhou
PowerdbyTCPDF(ww.tcpdf.org) *These authors contributed equally to this work
O r i g i n a l; r e s e a r c h
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Background: The ability to evaluate the prognosis of hepatocellular carcinoma (HCC)
following hepatectomy using biological markers is of great importance.
Materials and methods: In this study, we collected samples from 54 patients with HCC
after hepatectomy. Immunohistochemistry was used to detect the expression of Sema3C and
MFN2 in the HCC samples.
Results: Immunohistochemistry results showed that Sema3C and MFN2 co-expression was
significantly associated with tumor size. In addition, a significant association between high
Sema3C and low MFN2 levels and shorter overall survival was noted, when Sema3C and
MFN2 co-expression was analyzed.
Conclusion: The results suggest that the correlative expression level of Sema3C and MFN2
has a strong value in the prognosis of patients with HCC following hepatectomy.
Keywords: Sema3C, MFN2, hepatocellular carcinoma (HCC), prognosis, survival analysis
Introduction
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. It is
currently the third leading cause of cancer mortality, contributing to half a million
deaths each year. Although there have been many advances in HCC therapeutic
strategies over the past few years, the overall prognosis has not improved for cases
that present with advanced or terminal stage disease at diagnosis. Therefore, besides
novel markers, new and useful prognostic methods, in particular those specific for liver
cancer, would clearly be of great benefit. Consequently, the identification of biological
markers that can contribute to the evaluative prognosis of HCC after hepatectomy
is necessary.
Class 3 secreted semaphorins (Sema3 proteins) are a group of seven widely
expressed chemotropic factors, from Sema3A to Sema3G, with repulsive and
attractive activities.1 All Sema3 proteins analyzed to date (ie, Sema3A, Sema3B,
Sema3D, Sema3E, Sema3F, and Sema3G) inhibit cell migration and seem to have
antitumor properties.2 For example, Sema3A has been shown to inhibit the migration
of breast cancer cells3 and to block tumor growth in vivo.4 In contrast to other class 3
semaphorins, Sema3C has been poorly characterized. It has been shown to have high
level of expression in various types of tumor cells; a correlation between its expression
and tumor development and progression has been reported.5,6 It can promote tumor
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migration and is highly expressed in metastatic tumor cells,
such as prostate cancer cells.7,8 Concurrent Sema3C-positive
and Sema3A-, 3B-, and 3E-negative staining is associated
with adverse prognoses in low- and intermediate-risk patients
with prostate cancer after radical prostatectomy.9
Mitofusin-2 (MFN2), an integral outer mitochondrial
membrane protein consisting of 757 residues in humans,10
is associated with mitochondrial fusion processes. MFN2
plays an important role in the development of many tumor
types. It has been reported that MFN2 expression was
significantly higher in lung adenocarcinoma tissues than in
adjacent normal tissues.11 However, another report showed
that MFN2 immunostaining was very weak in HCC tissues,
and patients with HCC with lower MFN2 expression had
a poorer prognosis.12 MFN2 has been shown to induce
apoptosis in HCC cells, but the exact molecular mechanism
remains unclear.
The exact roles of Sema3C and MFN2 in HCC remain
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Subjects and methods
study subjects
HCC tissue microarrays were obtained from Shanghai
Outdo Biotech Co., Ltd. (Shanghai, People’s Republic of
China). Letters of consent were obtained from all patients,
and the experimental protocols were approved by the ethics
committee of Sir Run Run Shaw Hospital of Zhejiang
University. Irregular/segment/hemihepatectomy was
performed for patients by the size and location of the tumor, with
surgical margins above 1–2 cm. Patient charts were reviewed
to obtain relevant clinical data, including age, sex, tumor
size, alpha-fetoprotein, cirrhosis, hepatitis B virus surface
antigen (HBsAg), vascular invasion, TNM (tumor, nodes,
(...truncated)