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Laser microdissection expression profiling of marginal edges of colorectal tumours reveals evidence of increased lactate metabolism in the aggressive phenotype
  1. Christopher C Thorn (christhorn77{at}yahoo.com)
  1. University of Leeds, United Kingdom
    1. Tom C Freeman (tfreeman{at}staffmail.ed.ac.uk)
    1. University of Edinburgh, United Kingdom
      1. Nigel Scott (nigel.scott{at}leedsth.nhs.uk)
      1. Leeds Teaching Hospitals NHS Trust, United Kingdom
        1. P J Guillou (p.j.guillou{at}leeds.ac.uk)
        1. St. James's University Hospital, United Kingdom
          1. David Jayne (d.g.jayne{at}leeds.ac.uk)
          1. University of Leeds, United Kingdom

            Abstract

            Background: The morphology of the invasive margin in colorectal cancer (CRC) can be described as either pushing or infiltrative. These phenotypes carry prognostic significance, particularly in node negative disease, and provide an excellent model for the study of invasive behaviour in vivo.

            Methods: The marginal edges of 16 stage-matched tumours exhibiting these contrasting growth patterns were microdissected. The extracted was mRNA amplified and hybridised to a 9546 feature oligonucleotide array. Selected differentials were validated using real time PCR and protein product interrogated by immunohistochemistry.

            Results: After stringent quality control and filtering of data generated, 39 genes were identified as being significantly differentially expressed between the two types of marginal edge. Several genes involved in cellular metabolism were identified as differentials including lactate dehydrogenase B (LDHB) and modulators of glucose transport.

            Conclusions: The LDH expression profile differs between the invasive phenotypes. A hypothesis is proposed in which altered metabolism is a cause of contrasting invasive behaviour independent of the hypoxia inducible factor (HIF1A) mediated hypoxic response, consistent with the Warburg phenomenon.

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