Nerea Matamala1, María Teresa Vargas2, Ricardo González-Cámpora2, Rebeca Miñambres3, José Ignacio Arias4, Primitiva Menéndez5, Eduardo Andrés-León6, Gonzalo Gómez-López6, Kira Yanowsky1, Julio Calvete-Candenas7, Lucía Inglada-Pérez8, Beatriz Martínez-Delgado9, Javier Benítez10. 1. Human Cancer Genetics Programme and. 2. Pathology Service and. 3. Projects Unit, Sistemas Genómicos, Valencia, Spain; 4. Surgery Service and. 5. Pathology Service, Hospital Monte Naranco, Oviedo, Spain; 6. Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; 7. Medical Oncology Service, Hospital Virgen de la Macarena, Sevilla, Spain; 8. Human Cancer Genetics Programme and Spanish Network in Rare Diseases (CIBERER), Madrid, Spain; 9. Molecular Genetics Unit, Research Institute of Rare Diseases (IIER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. 10. Human Cancer Genetics Programme and Spanish Network in Rare Diseases (CIBERER), Madrid, Spain; jbenitez@cnio.es.
Abstract
BACKGROUND: The identification of novel biomarkers for early breast cancer detection would be a great advance. Because of their role in tumorigenesis and stability in body fluids, microRNAs (miRNAs) are emerging as a promising diagnostic tool. Our aim was to identify miRNAs deregulated in breast tumors and evaluate the potential of circulating miRNAs in breast cancer detection. METHODS: We conducted miRNA expression profiling of 1919 human miRNAs in paraffin-embedded tissue from 122 breast tumors and 11 healthy breast tissue samples. Differential expression analysis was performed, and a microarray classifier was generated. The most relevant miRNAs were analyzed in plasma from 26 healthy individuals and 83 patients with breast cancer (36 before and 47 after treatment) and validated in 116 healthy individuals and 114 patients before treatment. RESULTS: We identified a large number of miRNAs deregulated in breast cancer and generated a 25-miRNA microarray classifier that discriminated breast tumors with high diagnostic sensitivity and specificity. Ten miRNAs were selected for further investigation, of which 4 (miR-505-5p, miR-125b-5p, miR-21-5p, and miR-96-5p) were significantly overexpressed in pretreated patients with breast cancer compared with healthy individuals in 2 different series of plasma. MiR-505-5p and miR-96-5p were the most valuable biomarkers (area under the curve 0.72). Moreover, the expression levels of miR-3656, miR-505-5p, and miR-21-5p were decreased in a group of treated patients. CONCLUSIONS: Circulating miRNAs reflect the presence of breast tumors. The identification of deregulated miRNAs in plasma of patients with breast cancer supports the use of circulating miRNAs as a method for early breast cancer detection.
BACKGROUND: The identification of novel biomarkers for early breast cancer detection would be a great advance. Because of their role in tumorigenesis and stability in body fluids, microRNAs (miRNAs) are emerging as a promising diagnostic tool. Our aim was to identify miRNAs deregulated in breast tumors and evaluate the potential of circulating miRNAs in breast cancer detection. METHODS: We conducted miRNA expression profiling of 1919 human miRNAs in paraffin-embedded tissue from 122 breast tumors and 11 healthy breast tissue samples. Differential expression analysis was performed, and a microarray classifier was generated. The most relevant miRNAs were analyzed in plasma from 26 healthy individuals and 83 patients with breast cancer (36 before and 47 after treatment) and validated in 116 healthy individuals and 114 patients before treatment. RESULTS: We identified a large number of miRNAs deregulated in breast cancer and generated a 25-miRNA microarray classifier that discriminated breast tumors with high diagnostic sensitivity and specificity. Ten miRNAs were selected for further investigation, of which 4 (miR-505-5p, miR-125b-5p, miR-21-5p, and miR-96-5p) were significantly overexpressed in pretreated patients with breast cancer compared with healthy individuals in 2 different series of plasma. MiR-505-5p and miR-96-5p were the most valuable biomarkers (area under the curve 0.72). Moreover, the expression levels of miR-3656, miR-505-5p, and miR-21-5p were decreased in a group of treated patients. CONCLUSIONS: Circulating miRNAs reflect the presence of breast tumors. The identification of deregulated miRNAs in plasma of patients with breast cancer supports the use of circulating miRNAs as a method for early breast cancer detection.
Authors: Jeanne S Mandelblatt; Natasha K Stout; Clyde B Schechter; Jeroen J van den Broek; Diana L Miglioretti; Martin Krapcho; Amy Trentham-Dietz; Diego Munoz; Sandra J Lee; Donald A Berry; Nicolien T van Ravesteyn; Oguzhan Alagoz; Karla Kerlikowske; Anna N A Tosteson; Aimee M Near; Amanda Hoeffken; Yaojen Chang; Eveline A Heijnsdijk; Gary Chisholm; Xuelin Huang; Hui Huang; Mehmet Ali Ergun; Ronald Gangnon; Brian L Sprague; Sylvia Plevritis; Eric Feuer; Harry J de Koning; Kathleen A Cronin Journal: Ann Intern Med Date: 2016-01-12 Impact factor: 25.391