What makes a blood cell based miRNA expression pattern disease specific? - A miRNome analysis of blood cell subsets in lung cancer patients and healthy controls
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Petra Leidinger1,*, Christina Backes2,*, Indra N. Dahmke3, Valentina Galata2, Hanno Huwer4, Ingo Stehle5, Robert Bals5, Andreas Keller2, Eckart Meese1
1Institute of Human Genetics, Medical School, Saarland University, Building 60, 66421 Homburg/Saar, Germany
2Department of Clinical Bioinformatics, Saarland University, Building E2.1, 66123 Saarbrücken, Germany
3Institute for Clinical and Experimental Surgery, Saarland University, Building 65, 66421 Homburg/Saar, Germany
4Department of Thoracic Surgery, Voelklingen Heart Center, 66333 Voelklingen Germany
5Department of Pneumology, Medical School, Saarland University, Building 91, 66421 Homburg/Saar, Germany
*Equally contributed as first authors
Dr. Petra Leidinger, e-mail: [email protected]
Key words: microRNA, leukocytes, lung cancer, microarray, cell separation
Received: July 16, 2014 Accepted: August 28, 2014 Published: September 19, 2014
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.
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