title: Decreased expression of XPO4 is associated with poor prognosis in hepatocellular carcinoma.
abstract: OBJECTIVE
  Exportin 4 (XPO4) is a recently-discovered candidate tumor-suppressor gene identified in a liver cancer mouse model. To investigate the role of XPO4 in hepatocellular carcinoma (HCC) pathogenesis, we determined XPO4 expression and its correlation to prognosis in human primary HCC.
  
  
  METHODS
  The XPO4 mRNA transcription level in HCC cell lines and tissue samples were detected by real-time quantitative polymerase chain reaction (PCR). XPO4 protein expression in 123 primary HCC clinical surgical specimens were analyzed by immunohistochemical detection.
  
  
  RESULTS
  Real-time quantitative PCR showed a decrease in XPO4 expression in HCC cell lines BEL-7402, Hep-G2, and SK-hep1 compared to the normal liver cell line LO2. Decreased XPO4 mRNA was also found in the majority of tumor tissues compared with matched non-tumor liver tissues (P = 0.004). Immunohistochemical detection revealed that XPO4 expression was reduced in 51 of 123 (41.5%) tumor resection samples compared with adjunct non-tumor tissues. We also found XPO4 expression to be significantly correlated with tumor size (P = 0.045) and histopathological classification (P = 0.004). Kaplan-Meier survival curves showed that the downregulation of XPO4 resulted in a significantly poor prognosis (P = 0.008, log-rank test), and multivariate Cox's analysis showed that XPO4 expression was an independent prognostic factor for overall survival of HCC patients (P = 0.013).
  
  
  CONCLUSIONS
  Our data suggest that XPO4 could be involved in the progression of human HCC and could serve as a potential target for gene therapy in the treatment of HCC.
authors.affiliation: The State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Liang
authors.forename: Ke
authors.initials: K
authors.lastname: Pan
authors.forename: Min-Shan
authors.initials: MS
authors.lastname: Chen
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhao
authors.forename: Jian-Cong
authors.initials: JC
authors.lastname: Sun
authors.forename: Yi-Bing
authors.initials: YB
authors.lastname: Chen
authors.forename: Hai-Qing
authors.initials: HQ
authors.lastname: Ma
authors.forename: Qi-Jing
authors.initials: QJ
authors.lastname: Wang
authors.forename: Jian-Chuan
authors.initials: JC
authors.lastname: Xia
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D002681:China; D015536:Down-Regulation; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D028884:Karyopherins; D012333:RNA, Messenger; C414440:Xpo4 protein, human