Abstract
There is evidence of blood-borne miRNA signatures for various human diseases. To dissect the origin of disease-specific miRNA expression in human blood, we separately analyzed the miRNome of different immune cell subtypes, each in lung cancer patients and healthy individuals. Each immune cell type revealed a specific miRNA expression pattern also dependinging on the cell origin, line of defense, and function. The overall expression pattern of each leukocyte subtype showed great similarities between patients and 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 leukocyte subtype comparisons of 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. 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.
Highlights
MicroRNAs are tiny molecules with huge impact on the function of the single cell, and the complete organism, as they play an important role in regulation of gene expression in physiological and pathophysiological conditions
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 leukocyte subtype comparisons of cancer versus controls
In our former studies, we showed that whole blood samples of lung cancer patients can be separated from those of healthy control individuals with high accuracies between 87% and 95% depending on the set of differentially expressed miRNAs used for classification [10, 13]
Summary
MicroRNAs (miRNAs) are tiny molecules (around 20 nucleotides) with huge impact on the function of the single cell, and the complete organism, as they play an important role in regulation of gene expression in physiological and pathophysiological conditions. In our previous studies we investigated the miRNA expression pattern in blood samples from patients suffering from different www.impactjournals.com/oncotarget non-cancer and cancer diseases, including lung cancer [8,9,10,11,12,13,14]. In our former studies, we showed that whole blood samples of lung cancer patients can be separated from those of healthy control individuals with high accuracies between 87% and 95% depending on the set of differentially expressed miRNAs used for classification [10, 13]. To the best of our knowledge, there is no study investigating the miRNA expression pattern of specific immune cell subsets in patients with cancers other than leukemia
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