Journal Article

Whole blood microRNAs as potential biomarkers in post-operative early breast cancer patients

Brigitte Rack, Thomas W. P. Friedl, Marianna Alunni-Fabbroni, Tanja Fehm, Ralf Lorenz, Elisabeth Trapp, Wolfgang Janni, Sven Mahner, Leonie Majunke, Andreas Schneeweiss, Marie Tzschaschel, Thomas L. Beck, Peter A. Fasching

2018

Overview

Background microRNAs (miRNAs) are considered promising cancer biomarkers, showing high reliability, sensitivity and stability. Our study aimed to identify associations between whole blood miRNA profiles, presence of circulating tumor cells (CTCs) and clinical outcome in post-operative early breast cancer patients (EBC) to assess the utility of miRNAs as prognostic markers in this setting. Method A total of 48 post-operative patients, recruited in frame of the SUCCESS A trial, were included in this retrospective study and tested with a panel of 8 miRNAs (miR-10b, −19a, − 21, − 22, −20a, − 127, − 155, −200b). Additional 17 female healthy donors with no previous history of cancer were included in the study as negative controls. Blood samples were collected at different time points (pre-adjuvant therapy, post-adjuvant therapy, 2 years follow up), total RNA was extracted and the relative concentration of each miRNA was measured by quantitative PCR and compared in patients stratified on blood collection time or CTC detection. Furthermore, we compared miRNA profiles of patients, for each time point separately, and healthy donors. CTCs were visualized and quantified with immunocytochemistry analysis. Data were analyzed using non-parametric statistical tests. Results In our experimental system, miR-19a, miR-22 and miR-127 showed the most promising results, differentiating patients at different time points and from healthy controls, while miR-20a, miR-21 and miR-200b did not show any difference among the different groups. miR-10b and miR-155 were never detectable in our experimental system. With respect to patients’ clinical characteristics, we found a significant correlation between miR-200b and lymph node status and between miR-20a and tumor type. Furthermore, miR-127 correlated with the presence of CTCs. Finally, we found a borderline significance between Progression Free Survival and miR-19a levels. Conclusions This pilot study suggests that profiling whole blood miRNAs could help to better stratify post-operative EBC patients without any sign of metastasis to prevent later relapse or metastatic events.

• Publisher: Springer Science and Business Media LLC,BioMed Central,BioMed Central Ltd,BMC
• Subject: 610 Medical sciences Medicine / Adult / Aged / Analysis / Biological markers / Biomarkers, Tumor / Biomarkers, Tumor - blood / Biomarkers, Tumor - genetics / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms / Breast Neoplasms - blood / Breast Neoplasms - genetics / Breast Neoplasms - surgery / Cancer patients / Cancer Research / Care and treatment / Circulating tumor cell / Disease-Free Survival / Early breast cancer / Female / Gene Expression Profiling / Gene Expression Profiling - methods / Gene Expression Regulation, Neoplastic / Health aspects / Health Promotion and Disease Prevention / Humans / Immune system / Medicine/Public Health / Medizinische Fakultät / MicroRNA / MicroRNAs / MicroRNAs - blood / MicroRNAs - genetics / Middle Aged / Neoplasms. Tumors. Oncology. Including cancer and carcinogens / Neoplastic Cells, Circulating / Neoplastic Cells, Circulating - metabolism / Neoplastic Cells, Circulating - pathology / Oncology / Pilot Projects / Postoperative Period / Prognosis / RC254-282 / Research Article / Retrospective Studies / Surgical Oncology / Translational oncology / Tumor marker