title: MicroRNA-143 is a putative predictive factor for the response to fluoropyrimidine-based chemotherapy in patients with metastatic colorectal cancer.
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.
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: Simmer
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Sabine
authors.initials: S
authors.lastname: Venderbosch
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jeroen R
authors.initials: JR
authors.lastname: Dijkstra
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Vink-Börger
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University of München, München, Germany.
authors.forename: Claudius
authors.initials: C
authors.lastname: Faber
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Leonie J
authors.initials: LJ
authors.lastname: Mekenkamp
authors.affiliation: Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Miriam
authors.initials: M
authors.lastname: Koopman
authors.affiliation: Department for Health Evidence, Section Biostatistics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Anton F
authors.initials: AF
authors.lastname: De Haan
authors.affiliation: Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: Punt
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Iris D
authors.initials: ID
authors.lastname: Nagtegaal
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine / Q000008:administration & dosage; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000077146:Irinotecan; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D015337:Multicenter Studies as Topic; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016032:Randomized Controlled Trials as Topic
chemical_list: D014408:Biomarkers, Tumor; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000069287:Capecitabine; D000077146:Irinotecan; D002166:Camptothecin
keywords: biomarker; chemotherapy; colorectal cancer; fluoropyrimidine; microRNA