title: CD146 promotes metastasis and predicts poor prognosis of hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recurrence and metastasis after curative resection remain critical obstacles in HCC treatment. CD146 predicted poor prognosis of a variety of cancers including melanoma, breast tumors, prostate cancer, and gastric cancer. However, the role of CD146 in HCC has not yet been systematically explored.
  
  
  METHODS
  To investigate the role of CD146 in HCC, we evaluated its expression in HCC tissues and HCC cell lines using real-time PCR and western blotting (WB). Second, we established HCC cell lines that stably overexpressed and interfered CD146 and explored the function of CD146 in HCC in vitro and in vivo. Third, we conducted microarray analysis to investigate the potential mechanism by identifying differentially expressed genes. Last, follow ups were conducted to help uncover the connection of CD146 expression and the prognosis of HCC patients.
  
  
  RESULTS
  We found that CD146 was overexpressed in HCC tissues and that high CD146 expression predicted poor overall survival time and shorter recurrence period in HCC patients. In vitro and in vivo experiments indicated that CD146 promoted migration and invasion of HCC cell lines. Further study indicated that CD146 promoted epithelial mesenchymal transition (EMT), IL-8 upregulation, and STAT1 downregulation. CD146 was upregulated in HCC tissues and cell lines.
  
  
  CONCLUSIONS
  CD146 promoted metastasis of HCC cells and predicted poor prognosis of HCC patients. CD146 induced EMT, and IL-8 upregulation and STAT1 downregulation may be the potential underlying mechanism. The exact mechanism still needs further investigation.
authors.affiliation: Department of Hepatobiliary Surgery, Clinical Medical College of Yangzhou University, Yangzhou, P.R. China. jgqing2003@hotmail.com.|Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health; Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China. jgqing2003@hotmail.com.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health; Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China. zhanglongsurgeon@163.com.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health; Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China. zhuqin19@163.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Hepatobiliary Surgery, Clinical Medical College of Yangzhou University, Yangzhou, P.R. China. bdsno1@hotmail.com.
authors.forename: Dousheng
authors.initials: D
authors.lastname: Bai
authors.affiliation: Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health; Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China. zcy2732@sina.com.
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health; Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China. wangxh@njmu.edu.cn.
authors.forename: Xuehao
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D051929:CD146 Antigen / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051929:CD146 Antigen; C508606:CXCL8 protein, human; D016209:Interleukin-8; C497902:MCAM protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human