Oncotarget

Clinical Research Papers:

MicroRNA-143 is a putative predictive factor for the response to fluoropyrimidine-based chemotherapy in patients with metastatic colorectal cancer

Femke Simmer, Sabine Venderbosch, Jeroen R. Dijkstra, Elisa M. Vink-Börger, Claudius Faber, Leonie J. Mekenkamp, Miriam Koopman, Anton F. De Haan, Cornelis J. Punt and Iris D. Nagtegaal _

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Oncotarget. 2015; 6:22996-23007. https://doi.org/10.18632/oncotarget.4035

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Abstract

Femke Simmer1, Sabine Venderbosch1,2, Jeroen R. Dijkstra1, Elisa M. Vink-Börger1, Claudius Faber3, Leonie J. Mekenkamp1, Miriam Koopman4, Anton F. De Haan5, Cornelis J. Punt2 and Iris D. Nagtegaal1

1 Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands

2 Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

3 Institute of Pathology, Ludwig-Maximilians-University of München, München, Germany

4 Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands

5 Department for Health Evidence, Section Biostatistics, Radboud University Medical Center, Nijmegen, The Netherlands

Correspondence to:

Iris D. Nagtegaal, email:

Keywords: microRNA; biomarker; chemotherapy; fluoropyrimidine; colorectal cancer

Received: March 10, 2015 Accepted: April 10, 2015 Published: May 08, 2015

Abstract

Approximately half of the colorectal cancer (CRC) patients develop metastatic disease. Fluoropyrimidine-based chemotherapy forms the backbone of treatment in these patients. However, the response to this therapy varies between individuals. Therefore, an important challenge in CRC research is to identify biomarkers that are predictive of this response. In this study, we explored the potential of miRNAs, and the miRNA producing protein Dicer, as biomarkers that can predict chemo-sensitivity to fluoropyrimidine chemotherapy in patients with metastatic colorectal cancer (mCRC). We analyzed the levels of 22 miRNAs and the Dicer protein in primary tumors from patients with mCRC who were treated with first-line capecitabine monotherapy within the CAIRO trial of the Dutch Colorectal Cancer Group. Correlation between the expression status of miRNAs or Dicer in primary tumors and the progression free survival (PFS) were investigated. Patients with low expression of miR-143 in their primary tumor had increased median PFS compared to those with high expression of miR-143. Furthermore, FXYD3, an ion transport regulator and a putative target of miR-143, also showed an association with PFS. These findings warrant further studies to investigate the relationship between miR-143, FXYD3 and fluoropyrimidines, and the clinical utility of miR-143 as biomarker.


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