title: Circulating miRNAs with prognostic value in metastatic breast cancer and for early detection of metastasis.
abstract: Metastasis is the principal cause of high morbidity and mortality among breast cancer (BC) patients. Identification of markers that can be routinely monitored to predict onset of metastasis in BC patients and prognosis of metastatic breast cancer (MBC) patients would increase their median survival. In this study, plasma miRNAs of 40 MBC patients were profiled by TaqMan low density arrays and miRNAs with prognostic capacity were identified. The candidates were validated initially in the samples of 237 MBC patients and subsequently in 335 samples from an independent study cohort of BC patients. Sixteen miRNAs were established to be significantly associated with overall survival, and were termed as prognostic miRNA panel template (PROMPT). These included miR-141, miR-144, miR-193b, miR-200a, miR-200b, miR-200c, miR-203, miR-210, miR-215, miR-365, miR-375, miR-429, miR-486-5p, miR-801, miR-1260 and miR-1274a. Additionally, 11 of these miRNAs were also associated with progression-free survival. Their prognostic significance was further confirmed in samples from a second study cohort of BC patients. In addition, miR-200a, miR-200b, miR-200c, miR-210, miR-215 and miR-486-5p were found to be significantly associated with onset of metastasis up to 2 years prior to clinical diagnosis in BC patients. We have thus identified panels of miRNAs, which include metastasis promoting miR-200 family and miR-203, as well as oncogenic and tumor-suppressive miRNAs, that can serve as prognostic markers for MBC, and early detection markers of metastasis in BC.
authors.affiliation: Department of Molecular Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany, Department of Gynecology and Obstetrics, Molecular Biology of Breast Cancer.
authors.forename: Dharanija
authors.initials: D
authors.lastname: Madhavan
authors.affiliation: Department of Molecular Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany, Department of Gynecology and Obstetrics, Molecular Biology of Breast Cancer, patrick.pku@gmail.com.
authors.forename: Cike
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Gynecology and Obstetrics, National Center for Tumor Diseases, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Wallwiener
authors.affiliation: Division of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany, Department of Biostatistics, Oslo Center for Biostatistics and Epidemiology, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
authors.forename: Manuela
authors.initials: M
authors.lastname: Zucknick
authors.affiliation: Department of Gynecology and Obstetrics, National Center for Tumor Diseases, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Nees
authors.affiliation: Department of Gynecology and Obstetrics.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schott
authors.affiliation: Division of Cancer Epidemiology, Department of Genetic Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Rudolph
authors.affiliation: Department of Tumor Biology, University Hospital Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.affiliation: Hi-STEM-Heidelberg Institute for Stem Cell Technology and Experimental Medicine GmbH, 69120 Heidelberg, Germany and Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
authors.affiliation: Department of Tumor Biology, University Hospital Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.affiliation: Department of Gynecology and Obstetrics.
authors.forename: Christof
authors.initials: C
authors.lastname: Sohn
authors.affiliation: Division of Cancer Epidemiology, Department of Genetic Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.affiliation: Department of Gynecology and Obstetrics, National Center for Tumor Diseases, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.affiliation: Department of Molecular Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany, Department of Gynecology and Obstetrics, Molecular Biology of Breast Cancer.
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D011379:Prognosis; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs