title: A core invasiveness gene signature reflects epithelial-to-mesenchymal transition but not metastatic potential in breast cancer cell lines and tissue samples.
abstract: BACKGROUND
  Metastases remain the primary cause of cancer-related death. The acquisition of invasive tumour cell behaviour is thought to be a cornerstone of the metastatic cascade. Therefore, gene signatures related to invasiveness could aid in stratifying patients according to their prognostic profile. In the present study we aimed at identifying an invasiveness gene signature and investigated its biological relevance in breast cancer.
  
  
  RESULTS
  We collected a set of published gene signatures related to cell motility and invasion. Using this collection, we identified 16 genes that were represented at a higher frequency than observed by coincidence, hereafter named the core invasiveness gene signature. Principal component analysis showed that these overrepresented genes were able to segregate invasive and non-invasive breast cancer cell lines, outperforming sets of 16 randomly selected genes (all P<0.001). When applied onto additional data sets, the expression of the core invasiveness gene signature was significantly elevated in cell lines forced to undergo epithelial-mesenchymal transition. The link between core invasiveness gene expression and epithelial-mesenchymal transition was also confirmed in a dataset consisting of 2420 human breast cancer samples. Univariate and multivariate Cox regression analysis demonstrated that CIG expression is not associated with a shorter distant metastasis free survival interval (HR = 0.956, 95%C.I. = 0.896-1.019, P = 0.186).
  
  
  CONCLUSIONS
  These data demonstrate that we have identified a set of core invasiveness genes, the expression of which is associated with epithelial-mesenchymal transition in breast cancer cell lines and in human tissue samples. Despite the connection between epithelial-mesenchymal transition and invasive tumour cell behaviour, we were unable to demonstrate a link between the core invasiveness gene signature and enhanced metastatic potential.
authors.affiliation: Translational Cancer Research Unit, Oncology Center, GZA Hospitals Sint-Augustinus, Antwerp, Belgium ; Department of oncology, KU Leuven, Leuven, Belgium.
authors.forename: Melike
authors.initials: M
authors.lastname: Marsan
authors.affiliation: Translational Cancer Research Unit, Oncology Center, GZA Hospitals Sint-Augustinus, Antwerp, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van den Eynden
authors.affiliation: Laboratory for Cancer Research and Clinical Oncology, University of Antwerp, Antwerp, Belgium.
authors.forename: Ridha
authors.initials: R
authors.lastname: Limame
authors.affiliation: Department of oncology, KU Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Neven
authors.affiliation: Translational Cancer Research Unit, Oncology Center, GZA Hospitals Sint-Augustinus, Antwerp, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Hauspy
authors.affiliation: Gynaecologic oncology, UZA, Antwerp, Belgium.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Van Dam
authors.affiliation: Department of oncology, KU Leuven, Leuven, Belgium.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.affiliation: Translational Cancer Research Unit, Oncology Center, GZA Hospitals Sint-Augustinus, Antwerp, Belgium.
authors.forename: Luc Y
authors.initials: LY
authors.lastname: Dirix
authors.affiliation: Translational Cancer Research Unit, Oncology Center, GZA Hospitals Sint-Augustinus, Antwerp, Belgium.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Vermeulen
authors.affiliation: Translational Cancer Research Unit, Oncology Center, GZA Hospitals Sint-Augustinus, Antwerp, Belgium ; Department of oncology, KU Leuven, Leuven, Belgium.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Van Laere
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D011379:Prognosis