title: Expression profiling of mitochondrial voltage-dependent anion channel-1 associated genes predicts recurrence-free survival in human carcinomas.
abstract: BACKGROUND
  Mitochondrial voltage-dependent anion channels (VDACs) play a key role in mitochondria-mediated apoptosis. Both in vivo and in vitro evidences indicate that VDACs are actively involved in tumor progression. Specifically, VDAC-1, one member of the VDAC family, was thought to be a potential anti-cancer therapeutic target. Our previous study demonstrated that the human gene VDAC1 (encoding the VDAC-1 isoform) was significantly up-regulated in lung tumor tissue compared with normal tissue. Also, we found a significant positive correlation between the gene expression of VDAC1 and histological grade in breast cancer. However, the prognostic power of VDAC1 and its associated genes in human cancers is largely unknown.
  
  
  METHODS
  We systematically analyzed the expression pattern of VDAC1 and its interacting genes in breast, colon, liver, lung, pancreatic, and thyroid cancers. The genes differentially expressed between normal and tumor tissues in human carcinomas were identified.
  
  
  RESULTS
  The expression level of VDAC1 was uniformly up-regulated in tumor tissue compared with normal tissue in breast, colon, liver, lung, pancreatic, and thyroid cancers. Forty-four VDAC1 interacting genes were identified as being commonly differentially expressed between normal and tumor tissues in human carcinomas. We designated VDAC1 and the 44 dysregulated interacting genes as the VDAC1 associated gene signature (VAG). We demonstrate that the VAG signature is a robust prognostic biomarker to predict recurrence-free survival in breast, colon, and lung cancers, and is independent of standard clinical and pathological prognostic factors.
  
  
  CONCLUSIONS
  VAG represents a promising prognostic biomarker in human cancers, which may enhance prediction accuracy in identifying patients at higher risk for recurrence. Future therapies aimed specifically at VDAC1 associated genes may lead to novel agents in the treatment of cancer.
authors.affiliation: Department of Physiology, College of Medicine, Chung-Ang University, Seoul, South Korea.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Ko
authors.affiliation: Research Center for Learning Sciences, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Wanjun
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Physiology, College of Medicine, Chung-Ang University, Seoul, South Korea.
authors.forename: Inja
authors.initials: I
authors.lastname: Lim
authors.affiliation: Department of Medicine, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Physiology, College of Medicine, Chung-Ang University, Seoul, South Korea.
authors.forename: Hyoweon
authors.initials: H
authors.lastname: Bang
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D019295:Computational Biology; D030561:Databases, Nucleic Acid; D004843:Epistasis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008928:Mitochondria / Q000235:genetics*; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D059467:Transcriptome; D050995:Voltage-Dependent Anion Channel 1 / Q000235:genetics*
chemical_list: D050995:Voltage-Dependent Anion Channel 1