Sources to variability in circulating human miRNA signatures

ABSTRACTAn increasing number of studies propose circulating microRNAs (miRNAs) as biomarkers for a large number of human diseases including cancer, cardiovascular diseases, neurologic pathologies and others. To further validate miRNA as biomarkers it is indispensable to understand the variability of circulating miRNAs in healthy individuals. We determined the longitudinal miRNomes of 90 serum samples from the Janus Serum Bank in Norway, which have been stored between 23 and 40 y at -25 °Celsius. We profiled 3 serum samples with microarrays for 30 individuals, each. For each individual the samples were collected with a time interval of approximately 5 y. This design allowed insights into inter-individual variability, age dependent miRNA variability and the impact of storage length and pre-processing. A significant proportion of the miRNome was affected by the age of the blood donor and a not negligible, albeit small, part of the miRNome by the storage time. A substantial part of miRNAs was differentially a...