Details

Autor(en) / Beteiligte

• Rasmussen, Mads H.
• Jensen, Niels F.
• Tarpgaard, Line S.
• Qvortrup, Camilla
• Rømer, Maria U.
• Stenvang, Jan
• Hansen, Tine P.
• Christensen, Lise L.
• Lindebjerg, Jan
• Hansen, Flemming
• Jensen, Benny V.
• Hansen, Torben F.
• Pfeiffer, Per
• Brünner, Nils
• Ørntoft, Torben F.
• Andersen, Claus L.

Titel

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

Ist Teil von

• Molecular oncology, 2013-06, Vol.7 (3), p.637-646

Ort / Verlag

United States: Elsevier B.V

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Wiley Online Library

Beschreibungen/Notizen

• 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. ► High miR-625-3p levels were associated with resistance to oxaliplatin based chemotherapy and a shortened overall survival. ► High miR-625-3p levels were not prognostic, but solely predictive of oxaliplatin response. ► miR-625-3p was up-regulated in an oxaliplatin resistant colon cancer cell line.