SLUG transcription factor: A pro-survival and prognostic factor in gastrointestinal stromal tumour

Research output: Contribution to journalArticle

Abstract

Background:The SLUG transcription factor has been linked with the KIT signalling pathway that is important for gastrointestinal stromal tumour (GIST) tumourigenesis. Its clinical significance in GIST is unknown.Methods:Influence of SLUG expression on cell proliferation and viability were investigated in GIST48 and GIST882 cell lines. The association between tumour SLUG expression in immunohistochemistry and recurrence-free survival (RFS) was studied in two clinical GIST series, one with 187 patients treated with surgery alone, and another one with 313 patients treated with surgery and adjuvant imatinib.Results:SLUG downregulation inhibited cell proliferation, induced cell death in both cell lines, and sensitised GIST882 cells to lower imatinib concentrations. SLUG was expressed in 125 (25.0%) of the 500 clinical GISTs evaluated, and expression was associated with several factors linked with unfavourable prognosis. SLUG expression was associated with unfavourable RFS both when patients were treated with surgery alone (HR=3.40, 95% CI=1.67-6.89, P=0.001) and when treated with surgery plus adjuvant imatinib (HR=1.83, 95% CI=1.29-2.60, P=0.001).Conclusions:GIST patients with high tumour SLUG expression have unfavourable RFS. SLUG may mediate pro-survival signalling in GISTs.

Details

Authors
  • Olli Pekka Pulkka
  • Bengt Nilsson
  • Maarit Sarlomo-Rikala
  • Peter Reichardt
  • Mikael Eriksson
  • Kirsten Sundby Hall
  • Eva Wardelmann
  • Aki Vehtari
  • Heikki Joensuu
  • Harri Sihto
Organisations
External organisations
  • Sahlgrenska University Hospital
  • HELIOS Klinikum Berlin-Buch
  • University Hospital Münster
  • Helsinki University Central Hospital
  • Skåne University Hospital
  • Oslo university hospital
  • Aalto University
  • University of Helsinki
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)1195-1202
JournalBritish Journal of Cancer
Volume116
Issue number9
Publication statusPublished - 2017 Apr 25
Publication categoryResearch
Peer-reviewedYes