title: Clinical significance of mitofusin-2 and its signaling pathways in hepatocellular carcinoma.
abstract: BACKGROUND
  The mitochondrial GTPase mitofusin-2 (MFN2) gene encodes a mitochondrial membrane protein that can induce apoptosis of hepatocellular carcinoma (HCC) via the mitochondrial apoptotic pathway, as validated in our previous research. However, little is known of the clinical significance of MFN2 expression and its signaling pathways in HCC.
  
  
  METHODS
  MFN2 mRNA expression in tumor and adjacent non-tumor tissues from 115 patients with HCC was investigated using quantitative real-time PCR. The association of the MFN2 mRNA expression level with clinical and pathological parameters was evaluated statistically, while a comparative microarray analysis was used to identify MFN2 signaling pathways in HepG2 cells.
  
  
  RESULTS
  MFN2 was significantly (p < 0.0001) downregulated in HCC tissues. Low MFN2 expression was significantly correlated with sex and preoperative alpha-fetoprotein (p < 0.05). Both a Kaplan-Meier survival curve and multivariate analyses showed that MFN2 was related to overall survival. A comparative gene expression microarray revealed 211 upregulated (58 %) and 153 downregulated (42 %) genes. Eighteen pathways were identified as the most significant pathways correlated with MFN2.
  
  
  CONCLUSIONS
  Low MFN2 expression in HCC indicated a worse overall survival. Crucial signaling molecules such as PI3K-AKT, cytokine receptor, and focal adhesion may participate in MFN2-mediated signaling pathway changes in HCC.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China.|Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, No. 79 Qingchun Road, Hangzhou, 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, No. 79 Qingchun Road, Hangzhou, 310003, China.
authors.forename: Yingsheng
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China.|Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, No. 79 Qingchun Road, Hangzhou, 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, No. 79 Qingchun Road, Hangzhou, 310003, China.
authors.forename: Dongkai
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China.|Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, No. 79 Qingchun Road, Hangzhou, 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, No. 79 Qingchun Road, Hangzhou, 310003, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, No. 79 Qingchun Road, Hangzhou, 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, No. 79 Qingchun Road, Hangzhou, 310003, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, No. 79 Qingchun Road, Hangzhou, 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, No. 79 Qingchun Road, Hangzhou, 310003, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Huang
authors.affiliation: Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, No. 79 Qingchun Road, Hangzhou, 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, No. 79 Qingchun Road, Hangzhou, 310003, China.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, No. 79 Qingchun Road, Hangzhou, 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, No. 79 Qingchun Road, Hangzhou, 310003, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China.|Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, No. 79 Qingchun Road, Hangzhou, 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, No. 79 Qingchun Road, Hangzhou, 310003, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China. wam@zju.edu.cn.|Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, No. 79 Qingchun Road, Hangzhou, 310003, China. wam@zju.edu.cn.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, No. 79 Qingchun Road, Hangzhou, 310003, China. wam@zju.edu.cn.
authors.forename: Weilin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China. shusenzheng@zju.edu.cn.|Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, No. 79 Qingchun Road, Hangzhou, 310003, China. shusenzheng@zju.edu.cn.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, No. 79 Qingchun Road, Hangzhou, 310003, China. shusenzheng@zju.edu.cn.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human
keywords: Hepatocellular carcinoma; MFN2; Network function; Overall survival