Luděk Záveský1,2, Eva Jandáková3, Vít Weinberger4, Luboš Minář4, Veronika Hanzíková5, Daniela Dušková5, Adéla Faridová6, Radovan Turyna6, Ondřej Slanař7, Aleš Hořínek8,9, Milada Kohoutová8. 1. Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague and General University Hospital in Prague, Albertov 4, 128 00, Prague, Czech Republic. ludek.zavesky@gmail.com. 2. Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague and General University Hospital in Prague, Albertov 4, 128 00, Prague, Czech Republic. ludek.zavesky@gmail.com. 3. Department of Pathology, Faculty of Medicine, Masaryk University and University Hospital Brno, Obilní trh 11, 602 00, Brno, Czech Republic. 4. Department of Obstetrics and Gynecology, Masaryk University and University Hospital Brno, Obilní trh 11, 602 00, Brno, Czech Republic. 5. Faculty Transfusion Center, General University Hospital in Prague, U Nemocnice 2, 128 08, Prague, Czech Republic. 6. Institute for Mother and Child Care, Podolské nábřeží 157/36, 147 00, Prague - Podolí, Czech Republic. 7. Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague and General University Hospital in Prague, Albertov 4, 128 00, Prague, Czech Republic. 8. Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague and General University Hospital in Prague, Albertov 4, 128 00, Prague, Czech Republic. 9. 3rd Department of Medicine, Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 2, Czech Republic.
Abstract
BACKGROUND: Breast cancer is a leading cause of cancer-related death in women. Most cases are invasive ductal carcinomas of no special type (NST breast carcinomas). METHODS AND RESULTS: In this prospective, multicentric biomarker discovery study, we analyzed the expression of small non-coding RNAs (mainly microRNAs) in plasma by qPCR and evaluated their association with NST breast cancer. Large-scale expression profiling and subsequent validations have been performed in patient and control groups and compared with clinicopathological data. Small nuclear U6 snRNA, miR-548b-5p and miR-451a have been identified as candidate biomarkers. U6 snRNA was remarkably overexpressed in all the validations, miR-548b-5p levels were generally elevated and miR-451a expression was mostly downregulated in breast cancer groups. Combined U6 snRNA/miR-548b-5p signature demonstrated the best diagnostic performance based on the ROC curve analysis with AUC of 0.813, sensitivity 73.1% and specificity 82.6%. There was a trend towards increased expression of both miR-548b-5p and U6 snRNA in more advanced stages. Further, increased miR-548b-5p levels have been partially associated with higher grades, multifocality, Ki-67 positivity, and luminal B rather than luminal A samples. On the other hand, an association has been observed between high miR-451a expression and progesterone receptor positivity, lower grade, unifocal samples, Ki-67-negativity, luminal A rather than luminal B samples as well as improved progression-free survival and overall survival. CONCLUSIONS: Our results indicated that U6 snRNA and miR-548b-5p may have pro-oncogenic functions, while miR-451a may act as tumor suppressor in breast cancer.
BACKGROUND: Breast cancer is a leading cause of cancer-related death in women. Most cases are invasive ductal carcinomas of no special type (NST breast carcinomas). METHODS AND RESULTS: In this prospective, multicentric biomarker discovery study, we analyzed the expression of small non-coding RNAs (mainly microRNAs) in plasma by qPCR and evaluated their association with NST breast cancer. Large-scale expression profiling and subsequent validations have been performed in patient and control groups and compared with clinicopathological data. Small nuclear U6 snRNA, miR-548b-5p and miR-451a have been identified as candidate biomarkers. U6 snRNA was remarkably overexpressed in all the validations, miR-548b-5p levels were generally elevated and miR-451a expression was mostly downregulated in breast cancer groups. Combined U6 snRNA/miR-548b-5p signature demonstrated the best diagnostic performance based on the ROC curve analysis with AUC of 0.813, sensitivity 73.1% and specificity 82.6%. There was a trend towards increased expression of both miR-548b-5p and U6 snRNA in more advanced stages. Further, increased miR-548b-5p levels have been partially associated with higher grades, multifocality, Ki-67 positivity, and luminal B rather than luminal A samples. On the other hand, an association has been observed between high miR-451a expression and progesterone receptor positivity, lower grade, unifocal samples, Ki-67-negativity, luminal A rather than luminal B samples as well as improved progression-free survival and overall survival. CONCLUSIONS: Our results indicated that U6 snRNA and miR-548b-5p may have pro-oncogenic functions, while miR-451a may act as tumor suppressor in breast cancer.
Authors: H J Burstein; G Curigliano; S Loibl; P Dubsky; M Gnant; P Poortmans; M Colleoni; C Denkert; M Piccart-Gebhart; M Regan; H-J Senn; E P Winer; B Thurlimann Journal: Ann Oncol Date: 2019-10-01 Impact factor: 32.976
Authors: C Marchiò; R Natrajan; K K Shiu; M B K Lambros; S M Rodriguez-Pinilla; D S P Tan; C J Lord; D Hungermann; K Fenwick; N Tamber; A Mackay; J Palacios; A Sapino; H Buerger; A Ashworth; J S Reis-Filho Journal: J Pathol Date: 2008-12 Impact factor: 7.996
Authors: A Goldhirsch; E P Winer; A S Coates; R D Gelber; M Piccart-Gebhart; B Thürlimann; H-J Senn Journal: Ann Oncol Date: 2013-08-04 Impact factor: 32.976