title: Expression of osteopontin coregulators in primary colorectal cancer and associated liver metastases.
abstract: BACKGROUND
  A transcription regulatory complex (TRC) that includes Ets1, Ets2, PEA3 and β-catenin/T-cell factors regulates osteopontin (OPN) that is implicated in colorectal cancer (CRC) dissemination. The consistency of OPN transcriptional control between primary CRC and metastases is unclear. This study investigates expression and prognostic significance of the OPN-TRC in primary human CRC and associated colorectal liver metastases (CRLM).
  
  
  METHODS
  Osteopontin-TRC factors were assayed by digital microscopy in 38 primary CRCs and matched CRLM specimens and assessed against clinical prognosis.
  
  
  RESULTS
  In primary CRC, OPN expression intensity correlated with that of its co-activators, PEA3 (r=0.600; P<0.01), Ets1 (r=0.552; P<0.01), Ets2 (r=0.521; P<0.01) and had prognostic significance. Osteopontin intensity in primary CRC inversely correlated with the interval between diagnosis and resection of CRLM. Overall OPN intensity was lower in CRLM than primary CRC and correlations with co-activators were weaker, for example, Ets1 (P=0.047), PEA3 (P=0.022) or nonsignificant (Ets2). The ratio of OPN expression in CRLM vs primary CRC had prognostic significance.
  
  
  CONCLUSIONS
  This study supports transcriptional control of OPN by known coregulators in both primary and secondary CRC. Weaker associations in CRLM suggest involvement of other unknown factors possibly from the liver microenvironment or resulting from additional genetic or epigenetic changes that drive tumour metastatic capability in OPN transcriptional control.
authors.affiliation: Clinical and Surgical Sciences (Surgery), The University of Edinburgh, Edinburgh EH8 9YL, Scotland, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Mole
authors.forename: C
authors.initials: C
authors.lastname: O'Neill
authors.forename: P
authors.initials: P
authors.lastname: Hamilton
authors.forename: B
authors.initials: B
authors.lastname: Olabi
authors.forename: V
authors.initials: V
authors.lastname: Robinson
authors.forename: L
authors.initials: L
authors.lastname: Williams
authors.forename: T
authors.initials: T
authors.lastname: Diamond
authors.forename: M
authors.initials: M
authors.lastname: El-Tanani
authors.forename: F C
authors.initials: FC
authors.lastname: Campbell
mesh_terms: D000368:Aged; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism; D050787:Proto-Oncogene Protein c-ets-2 / Q000378:metabolism; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin; C065788:transcription factor PEA3; D053495:Osteopontin