The evaluative value of Sema3C and MFN2 co-expression detected by immunohistochemistry for prognosis in hepatocellular carcinoma patients after hepatectomy

OncoTargets and Therapy, May 2016

The evaluative value of Sema3C and MFN2 co-expression detected by immunohistochemistry for prognosis in hepatocellular carcinoma patients after hepatectomy Xu Feng,1,* Kelei Zhu,1,2,* Jinghua Liu,1 Jiang Chen,1 Jiacheng Tang,3 Yuelong Liang,1 Renan Jin,1 Xiao Liang,1 Xiujun Cai1,3 1Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 2Department of General Surgery, Yinzhou People’s Hospital, Ningbo, 3Key Lab of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China *These authors contributed equally to this work 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

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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 - 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 8 1 0 2 l u J 3 1 n o 0 . 5 1 . 5 3 1 . 5 y b / m o c . s s e 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 .rvepdow l.ysneo uSnedmeate3rCmainneddM.IFnNth2isinst5u4dyc,awsees aonfaHlyCzeCdatnhde eexvpalrueassteiodnthoef /:ww luan prognoses of those patients. / s o ttp rs h pe from roF d e d a o l n w o d y p a r e h T d n a s t e g r a T o c n O 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)


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Xu Feng, Kelei Zhu, Jinghua Liu, Jiang Chen, Jiacheng Tang, Yuelong Liang, Renan Jin, Xiao Liang, Xiujun Cai. The evaluative value of Sema3C and MFN2 co-expression detected by immunohistochemistry for prognosis in hepatocellular carcinoma patients after hepatectomy, OncoTargets and Therapy, 2016, pp. 3213-3221, DOI: 10.2147/OTT.S98322