Meta-analysis and gene set analysis of archived microarrays suggest implication of the spliceosome in metastatic and hypoxic phenotypes.
We propose to make use of the wealth of underused DNA chip data available in public repositories to study the molecular mechanisms behind the adaptation of cancer cells to hypoxic conditions leading to the metastatic phenotype. We have developed new bioinformatics tools and adapted others to identify with maximum sensitivity those genes which are expressed differentially across several experiments. The comparison of two analytical approaches, based on either Over Representation Analysis or Functional Class Scoring, by a meta-analysis-based approach, led to the retrieval of known information about the biological situation - thus validating the model - but also more importantly to the discovery of the previously unknown implication of the spliceosome, the cellular machinery responsible for mRNA splicing, in the development of metastasis.
Microorganism Biology Research Unit -NARILIS, University of Namur, Namur, Belgium.
Bertrand
B
De Meulder
Microorganism Biology Research Unit -NARILIS, University of Namur, Namur, Belgium.
Fabrice
F
Berger
Sainte Justine University Hospital Center Research Center, University of Montreal, Montreal, Canada.
Eric
E
Bareke
Environmental and Evolutional Research Unit, University of Namur, Namur, Belgium.
Sophie
S
Depiereux
Cellular Biology Research Unit - NARILIS, University of Namur, Namur, Belgium.
Carine
C
Michiels
Microorganism Biology Research Unit -NARILIS, University of Namur, Namur, Belgium.
Eric
E
Depiereux
D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics; D017381:Spliceosomes / Q000235:genetics*