High expression of microRNA-625-3p is associated with poor response to first-line oxaliplatin based treatment of metastatic colorectal cancer

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  • Mads Heilskov Rasmussen
  • Niels Jensen, Institut for Sprog og Kultur, Denmark
  • Line Schmidt Tarpgaard, Onkologi, Denmark
  • Camilla Qvortrup, Onkologi, Denmark
  • Maria Unni Koefoed Rømer, 2012 Faggruppe Patobiologi, Denmark
  • Jan Stenvang, Sektion, Molecular Disease Biology, Denmark
  • Tine Hansen, Institut for Organisation, Denmark
  • Lise L Christensen
  • Jan Lindebjerg, Klinisk Patologi, Laboratoriecentret, Denmark
  • Flemming Hansen, Denmark
  • Benny V Jensen
  • ,
  • Torben F Hansen
  • ,
  • Per Pfeiffer, Onkologi, Denmark
  • Nils Brünner, Institut for Veterinær Sygdomsbiologi, LIFE, Københavns Universitet , Denmark
  • Torben F Orntoft
  • Claus L Andersen
The backbone of current cytotoxic treatment of metastatic colorectal cancer (mCRC) consists of a fluoropyrimidine together with either oxaliplatin (XELOX/FOLFOX) or irinotecan (XELIRI/FOLFIRI). With an overall objective response rate of approximately 50% for either treatment combination, a major unsolved problem is that no predictors of response to these treatments are available. To address this issue, we profiled 742 microRNAs in laser-capture microdissected cancer cells from responding and non-responding patients receiving XELOX/FOLFOX as first-line treatment for mCRC, and identified, among others, high expression of miR-625-3p, miR-181b and miR-27b to be associated with poor clinical response. In a validation cohort of 94 mCRC patients treated first-line with XELOX, high expression of miR-625-3p was confirmed to be associated with poor response (OR = 6.25, 95%CI [1.8; 21.0]). Independent analyses showed that miR-625-3p was not dysregulated between normal and cancer samples, nor was its expression associated with recurrence of stage II or III disease, indicating that miR-625-3p solely is a response marker. Finally, we also found that these miRNAs were up-regulated in oxaliplatin resistant HCT116/oxPt (miR-625-3p, miR-181b and miR-27b) and LoVo/oxPt (miR-181b) colon cancer cell lines as compared with their isogenic parental cells. Altogether, our results suggest an association between miR-625-3p and response to first-line oxaliplatin based chemotherapy of mCRC.
Original languageEnglish
JournalMolecular Oncology
Volume7
Issue3
Pages (from-to)637-646
Number of pages10
ISSN1574-7891
DOIs
Publication statusPublished - Jun 2013

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