What makes the blood cell-based miRNome disease specific? - miRNA analysis of leukocyte subsets in lung cancer patients and controls

Background: There is ample evidence of blood-born miRNA signatures for various human diseases. To dissect the origin of disease-specific miRNA expression in human blood cells, we separately analyzed the miRNome of eosinophilic and neutrophilic granulocytes, monocytes, B-cells, T-cells, and natural killer cells, each in lung cancer patients and healthy individuals. Results: We found specific miRNA expression patterns for each immune cell type and also depending on the cell origin, line of defense, and function. The overall expression pattern of each leukocyte subtype showed great similarities between lung cancer patients and healthy controls. However, for each cell subtype we identified miRNAs that were deregulated in lung cancer patients including hsa-miR-21, a well- known oncomiR associated with poor lung cancer prognosis that was up-regulated in all subtype comparisons of lung cancer versus controls. While the miRNome of cells of the adaptive immune system allowed only a weak separation between patients and controls, cells of the innate immune system allowed perfect or nearly perfect classification. Conclusions: Leukocytes of lung cancer patients show a cancer-specific miRNA expression profile. Our data also show that cancer specific miRNA expression pattern of whole blood samples are not determined by a single cell type. The data indicate that additional blood components, like erythrocytes, platelets, or exosomes might contribute to the disease specificity of a miRNA signature. We obtained EDTA and PAXgene blood from 7 healthy subjects and 7 lung cancer patients and isolated the CD3, CD19, CD15, CD14, and CD56 positive cell fractions from the EDTA blood samples to compare the miRNomes of the cell subsets of healthy individuals versus lung cancer patients.