Gene expression meta-analysis identifies VDAC1 as a predictor of poor outcome in early stage non-small cell lung cancer

Claire Grills, Puthen V. Jithesh, Jaine Blayney, Shu Dong Zhang, Dean A. Fennell

Research output: Contribution to journalArticle

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Abstract

Background: The bioenergetic status of non-small cell lung cancer correlates with tumour aggressiveness. The voltage dependent anion channel type 1 (VDAC1) is a component of the mitochondrial permeability transition pore, regulates mitochondrial ATP/ADP exchange suggesting that its over-expression could be associated with energy dependent processes including increased proliferation and invasiveness. To test this hypothesis, we conducted an in vivo geneexpression meta-analysis of surgically resected non-small cell lung cancer (NSCLC) using 602 individual expression profiles, to examine the impact of VDAC1 on survival. Methodology/Principal Findings: High VDAC1 expression was associated with shorter overall survival with hazard ratio (HR) = 0.6639 (95% confidence interval (CI) 0.4528 to 0.9721), p = 0.035352 corresponding to 52 versus 101 months. VDAC1 predicted shorter time to recurrence and was shown to be an independent prognostic factor compared with histology, gender, age, nodal stage and tumour stage in a Cox multivariate analysis. Supervised analysis of all the datasets identified a 6-gene signature comprising HNRNPC, HSPA4, HSPA9, UBE2D2, CSNK1A1 and G3BP1 with overlapping functions involving regulation of protein turnover, RAS-RAF-MEK pathway and transcription. VDAC1 predicted survival in breast cancer and myeloma and an unsupervised analysis revealed enrichment of the VDAC1 signature in specific subsets. Conclusions: In summary, gene expression analysis identifies VDAC1 gene expression as a predictor of poor outcome in NSCLC and other cancers and is associated with dysregulation of a conserved set of biological pathways, which may be causally associated with aggressive tumour behaviour.

Original languageEnglish
Article numbere14635
JournalPLoS One
Volume6
Issue number1
DOIs
Publication statusPublished - 2011
Externally publishedYes

Fingerprint

Voltage-Dependent Anion Channel 1
lung neoplasms
meta-analysis
Gene expression
Non-Small Cell Lung Carcinoma
anions
Meta-Analysis
Cells
Gene Expression
gene expression
Tumors
cells
neoplasms
Neoplasms
myeloma
Histology
Mitogen-Activated Protein Kinase Kinases
Transcription
protein metabolism
breast neoplasms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Gene expression meta-analysis identifies VDAC1 as a predictor of poor outcome in early stage non-small cell lung cancer. / Grills, Claire; Jithesh, Puthen V.; Blayney, Jaine; Zhang, Shu Dong; Fennell, Dean A.

In: PLoS One, Vol. 6, No. 1, e14635, 2011.

Research output: Contribution to journalArticle

Grills, Claire ; Jithesh, Puthen V. ; Blayney, Jaine ; Zhang, Shu Dong ; Fennell, Dean A. / Gene expression meta-analysis identifies VDAC1 as a predictor of poor outcome in early stage non-small cell lung cancer. In: PLoS One. 2011 ; Vol. 6, No. 1.
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