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

Mads Heilskov Rasmussen, Niels Jensen, Line Schmidt Tarpgaard, Camilla Qvortrup, Maria Unni Koefoed Rømer, Jan Stenvang, Tine P Hansen, Lise Christensen, Jan Lindebjerg, Flemming Hansen, Benny Jensen, Torben F Hansen, Per Pfeiffer, Nils Aage Brünner, Torben Falck Ørntoft, Claus L Andersen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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
Issue number3
Pages (from-to)637-646
Number of pages10
ISSN1574-7891
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Aged
  • Antineoplastic Agents
  • Antineoplastic Combined Chemotherapy Protocols
  • Cell Line, Tumor
  • Cohort Studies
  • Colon
  • Colorectal Neoplasms
  • Deoxycytidine
  • Drug Resistance, Neoplasm
  • Female
  • Fluorouracil
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs
  • Middle Aged
  • Organoplatinum Compounds
  • Rectum
  • Up-Regulation
  • Chemotherapy resistance
  • MicroRNA-625
  • XELOX/FOLFOX
  • Oxaliplatin
  • Metastatic colorectal cancer

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