title: Circulating MicroRNAs as easy-to-measure aging biomarkers in older breast cancer patients: correlation with chronological age but not with fitness/frailty status.
abstract: Circulating microRNAs (miRNAs) hold great promise as easily accessible biomarkers for diverse (patho)physiological processes, including aging. We have compared miRNA expression profiles in cell-free blood from older versus young breast cancer patients, in order to identify "aging miRNAs" that can be used in the future to monitor the impact of chemotherapy on the patient's biological age. First, we assessed 175 miRNAs that may possibly be present in serum/plasma in an exploratory screening in 10 young and 10 older patients. The top-15 ranking miRNAs showing differential expression between young and older subjects were further investigated in an independent cohort consisting of another 10 young and 20 older subjects. Plasma levels of miR-20a-3p, miR-30b-5p, miR106b, miR191 and miR-301a were confirmed to show significant age-related decreases (all p≤0.004). The remaining miRNAs included in the validation study (miR-21, miR-210, miR-320b, miR-378, miR-423-5p, let-7d, miR-140-5p, miR-200c, miR-374a, miR376a) all showed similar trends as observed in the exploratory screening but these differences did not reach statistical significance. Interestingly, the age-associated miRNAs did not show differential expression between fit/healthy and non-fit/frail subjects within the older breast cancer cohort of the validation study and thus merit further investigation as true aging markers that not merely reflect frailty.
authors.affiliation: Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hatse
authors.affiliation: Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Brouwers
authors.affiliation: Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium; Department of Internal Medicine, Istituto di Ricerca a Carattere Clinico e Scientifico (IRCCS), Azienda Ospedaliera Universitaria (AOU) San Martino Istituto Nazionale Tumori (IST), Genoa, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Dalmasso
authors.affiliation: Interuniversity Centre for Biostatistics and Statistical Bioinformatics, Leuven, Belgium.
authors.forename: Annouschka
authors.initials: A
authors.lastname: Laenen
authors.affiliation: Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium; Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Cindy
authors.initials: C
authors.lastname: Kenis
authors.affiliation: Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schöffski
authors.affiliation: Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Wildiers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010809:Physical Fitness
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs