title: Plasma microRNA panel for minimally invasive detection of breast cancer.
abstract: Over the last few years, circulating microRNAs (miRNAs) have emerged as promising novel and minimally invasive markers for various diseases, including cancer. We already showed that certain miRNAs are deregulated in the plasma of breast cancer patients when compared to healthy women. Herein we have further explored their potential to serve as breast cancer early detection markers in blood plasma. Circulating miR-127-3p, miR-376a and miR-652, selected as candidates from a miRNA array-based screening, were found to be associated with breast cancer for the first time (n = 417). Further we validated our previously reported circulating miRNAs (miR-148b, miR-376c, miR-409-3p and miR-801) in an independent cohort (n = 210) as elevated in the plasma of breast cancer patients compared to healthy women. We described, for the first time in breast cancer, an over-representation of deregulated miRNAs (miR-127-3p, miR-376a, miR-376c and miR-409-3p) originating from the chromosome 14q32 region. The inclusion of patients with benign breast tumors enabled the observation that miR-148b, miR-652 and miR-801 levels are even elevated in the plasma of women with benign tumors when compared to healthy controls. Furthermore, an analysis of samples stratified by cancer stage demonstrated that miR-127-3p, miR-148b, miR-409-3p, miR-652 and miR-801 can detect also stage I or stage II breast cancer thus making them attractive candidates for early detection. Finally, ROC curve analysis showed that a panel of these seven circulating miRNAs has substantial diagnostic potential with an AUC of 0.81 for the detection of benign and malignant breast tumors, which further increased to 0.86 in younger women (up to 50 years of age).
authors.affiliation: Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany ; Molecular Biology of Breast Cancer, University Women's Clinic, Heidelberg, Germany.
authors.forename: Katarina
authors.initials: K
authors.lastname: Cuk
authors.forename: Manuela
authors.initials: M
authors.lastname: Zucknick
authors.forename: Dharanija
authors.initials: D
authors.lastname: Madhavan
authors.forename: Sarah
authors.initials: S
authors.lastname: Schott
authors.forename: Michael
authors.initials: M
authors.lastname: Golatta
authors.forename: Jörg
authors.initials: J
authors.lastname: Heil
authors.forename: Frederik
authors.initials: F
authors.lastname: Marmé
authors.forename: Andrey
authors.initials: A
authors.lastname: Turchinovich
authors.forename: Peter
authors.initials: P
authors.lastname: Sinn
authors.forename: Christof
authors.initials: C
authors.lastname: Sohn
authors.forename: Hans
authors.initials: H
authors.lastname: Junkermann
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000175:diagnosis*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C547276:MIRN127 microRNA, human; C550570:MIRN148 microRNA, human; C573498:MIRN376C microRNA, human; C574011:MIRN652 microRNA, human; D035683:MicroRNAs