title: CISD2 associated with proliferation indicates negative prognosis in patients with hepatocellular carcinoma.
abstract: BACKGROUND
  An evolutionarily conserved gene, the CDGSH iron sulfur domain 2 (CISD2), functions to control mammalian life span and regulates human cells proliferation. However, the role of CISD2 in HCC remains unclear. This study was aimed at investigating the expression pattern and clinicopathological significance of CISD2 in patients with HCC.
  
  
  METHODS
  The mRNA and protein expression levels of CISD2 were analyzed in six HCC lines and eight paired hepatic cancer tumors by real-time PCR, Western blotting and immunohistochemical staining. Statistical analysis was used to evaluate the clinicopathological significance of CISD2 expression. Short hairpin RNA interfering approach was employed to suppress endogenous CISD2 expression in hepatic cancer cells to determine its role in proliferation.
  
  
  RESULTS
  CISD2 expression in liver cancer cell lines and tissues was significantly up-regulated at both the RNA and protein levels compared with that in normal cells and adjacent non-tumorous liver tissues (ANT). CISD2 was an independent prognostic factor for poor prognosis. It was correlated with tumor size (P=0.001), number of tumors (P=0.003), surgical margin (P=0.006), hepatitis B surface antigen (HBsAg) infection (P=0.002) and recurrence (P<0.001) of liver cancer. Multivariate analysis suggested that CISD2 expression was an independent prognostic indicator for the survival of patients with HCC. HCC patients with high CISD2 expression displayed a shorter overall survival and a higher recurrence rate than those with low CISD2 expression (P<0.05, respectively). Additionally, stable down-expression of CISD2 in hepatoma cells suppressed cell proliferation in vitro. Similarly, an in vivo assay showed that CISD2 down-regulation in hepatoma cells inhibited remarkably tumorigenic potential in tumor size and weight.
  
  
  CONCLUSIONS
  CISD2 protein may serve as a candidate prognostic marker and a novel therapeutic target for HCC and play an important role in promoting proliferation and enhanced progression of HCC.
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat-sen University Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat-sen University Guangzhou, China.
authors.forename: Shunli
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat-sen University Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat-sen University Guangzhou, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat-sen University Guangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Kuang
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat-sen University Guangzhou, China.
authors.forename: Shaoqiang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat-sen University Guangzhou, China.
authors.forename: Baogang
authors.initials: B
authors.lastname: Peng
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C523851:CISD2 protein, human; D008565:Membrane Proteins
keywords: CDGSH iron sulfur domain 2; hepatocellular carcinoma; prognostic marker; proliferation; therapeutic target