title: FBX8 Acts as an Invasion and Metastasis Suppressor and Correlates with Poor Survival in Hepatocellular Carcinoma.
abstract: F-box only protein 8 (FBX8), a novel component of F-box proteins, is lost in several cancers and has been associated with invasiveness of cancer cells. However, its expression pattern and role in the progression of hepatocellular carcinoma remain unclear. This study investigated the prognostic significance of FBX8 in hepatocellular carcinoma samples and analyzed FBX8 function in hepatocellular carcinoma cells by gene manipulation.
  
  
  
  The expression of FBX8 was detected in 120 cases of clinical paraffin-embedded hepatocellular carcinoma tissues, 20 matched pairs of fresh tissues and five hepatocellular carcinoma cell lines by immunohistochemistry with clinicopathological analyses, real-time RT-PCR or Western blot. The correlation of FBX8 expression with cell proliferation and invasion in five HCC cell lines was analyzed. Moreover, loss of function and gain of function assays were performed to evaluate the effect of FBX8 on cell proliferation, motility, invasion in vitro and metastasis in vivo.
  
  
  
  We found that FBX8 was obviously down-regulated in HCC tissues and cell lines (P<0.05). The FBX8 down-regulation correlated significantly with poor prognosis, and FBX8 status was identified as an independent significant prognostic factor. Over-expression of FBX8 decreased proliferation, migration and invasion in HepG2 and 97H cells, while knock-down of FBX8 in 7721 cells showed the opposite effect. FBX8 negatively correlated with cell proliferation and invasion in 7701, M3, HepG2 and 97H cell lines. In vivo functional assays showed FBX8 suppressed tumor growth and pulmonary metastatic potential in mice. Our results indicate that down-regulation of FBX8 significantly correlates with invasion, metastasis and poor survival in hepatocellular carcinoma patients. It may be a useful biomarker for therapeutic strategy and control in hepatocellular carcinoma treatment.
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou City, Guangdong Province, People's Republic of China ; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou City, Guangdong Province, People's Republic of China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
authors.forename: Yudan
authors.initials: Y
authors.lastname: Qiao
authors.forename: Jiang
authors.initials: J
authors.lastname: Yu
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ren
authors.forename: Jianmei
authors.initials: J
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zhang
authors.forename: Wenhui
authors.initials: W
authors.lastname: Ma
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Liang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009362:Neoplasm Metastasis / Q000503:physiopathology; D009368:Neoplasm Transplantation; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D044783:F-Box Proteins; C555947:FBXO8 protein, human