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 Frank Jensen; Line Schmidt Tarpgaard; Camilla Qvortrup; Maria Unni Koefoed Rømer; Jan Stenvang; Tine Plato Hansen; Lise Lotte Christensen; Jan Lindebjerg; Flemming Hansen; Benny V. Jensen; Torben F. Hansen; Per Pfeiffer; Nils Brünner; Torben Falck Ørntoft; Claus Lindbjerg Andersen

doi:10.1016/j.molonc.2013.02.016

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 Frank Jensen, Line Schmidt Tarpgaard, Camilla Qvortrup, Maria Unni Koefoed Rømer, Jan Stenvang, Tine Plato Hansen, Lise Lotte Christensen, Jan Lindebjerg, Flemming Hansen, Benny V. Jensen, Torben F. Hansen, Per Pfeiffer, Nils Brünner, Torben Falck Ørntoft, Claus Lindbjerg Andersen

70 Citations (Scopus)

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 language	English
Journal	Molecular Oncology
Volume	7
Issue number	3
Pages (from-to)	637-646
Number of pages	10
ISSN	1574-7891
DOIs	https://doi.org/10.1016/j.molonc.2013.02.016
Publication status	Published - Jun 2013

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Rasmussen, M. H., Jensen, N. F., Tarpgaard, L. S., Qvortrup, C., Rømer, M. U. K., Stenvang, J., Hansen, T. P., Christensen, L. L., Lindebjerg, J., Hansen, F., Jensen, B. V., Hansen, T. F., Pfeiffer, P., Brünner, N., Ørntoft, T. F., & Andersen, C. L. (2013). High expression of microRNA-625-3p is associated with poor response to first-line oxaliplatin based treatment of metastatic colorectal cancer. Molecular Oncology, 7(3), 637-646. https://doi.org/10.1016/j.molonc.2013.02.016

High expression of microRNA-625-3p is associated with poor response to first-line oxaliplatin based treatment of metastatic colorectal cancer. / Rasmussen, Mads Heilskov; Jensen, Niels Frank; Tarpgaard, Line Schmidt et al.

In: Molecular Oncology, Vol. 7, No. 3, 06.2013, p. 637-646.

Research output: Contribution to journal › Journal article › Research › peer-review

Rasmussen, MH, Jensen, NF, Tarpgaard, LS, Qvortrup, C, Rømer, MUK, Stenvang, J, Hansen, TP, Christensen, LL, Lindebjerg, J, Hansen, F, Jensen, BV, Hansen, TF, Pfeiffer, P, Brünner, N, Ørntoft, TF & Andersen, CL 2013, 'High expression of microRNA-625-3p is associated with poor response to first-line oxaliplatin based treatment of metastatic colorectal cancer', Molecular Oncology, vol. 7, no. 3, pp. 637-646. https://doi.org/10.1016/j.molonc.2013.02.016

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

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.",

author = "Rasmussen, {Mads Heilskov} and Jensen, {Niels Frank} and Tarpgaard, {Line Schmidt} and Camilla Qvortrup and R{\o}mer, {Maria Unni Koefoed} and Jan Stenvang and Hansen, {Tine Plato} and Christensen, {Lise Lotte} and Jan Lindebjerg and Flemming Hansen and Jensen, {Benny V.} and Hansen, {Torben F.} and Per Pfeiffer and Nils Br{\"u}nner and {\O}rntoft, {Torben Falck} and Andersen, {Claus Lindbjerg}",

year = "2013",

month = jun,

doi = "10.1016/j.molonc.2013.02.016",

language = "English",

volume = "7",

pages = "637--646",

journal = "Molecular Oncology",

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T1 - High expression of microRNA-625-3p is associated with poor response to first-line oxaliplatin based treatment of metastatic colorectal cancer

AU - Rasmussen, Mads Heilskov

AU - Jensen, Niels Frank

AU - Tarpgaard, Line Schmidt

AU - Qvortrup, Camilla

AU - Rømer, Maria Unni Koefoed

AU - Stenvang, Jan

AU - Hansen, Tine Plato

AU - Christensen, Lise Lotte

AU - Lindebjerg, Jan

AU - Hansen, Flemming

AU - Jensen, Benny V.

AU - Hansen, Torben F.

AU - Pfeiffer, Per

AU - Brünner, Nils

AU - Ørntoft, Torben Falck

AU - Andersen, Claus Lindbjerg

PY - 2013/6

Y1 - 2013/6

N2 - 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.

AB - 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.

U2 - 10.1016/j.molonc.2013.02.016

DO - 10.1016/j.molonc.2013.02.016

M3 - Journal article

C2 - 23506979

SN - 1574-7891

VL - 7

SP - 637

EP - 646

JO - Molecular Oncology

JF - Molecular Oncology

IS - 3

ER -

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

Abstract

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