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Toward the blood-borne miRNome of human diseases

Nature Methods volume 8, pages 841–843 (2011)Cite this article

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Abstract

In a multicenter study, we determined the expression profiles of 863 microRNAs by array analysis of 454 blood samples from human individuals with different cancers or noncancer diseases, and validated this 'miRNome' by quantitative real-time PCR. We detected consistently deregulated profiles for all tested diseases; pathway analysis confirmed disease association of the respective microRNAs. We observed significant correlations (P = 0.004) between the genomic location of disease-associated genetic variants and deregulated microRNAs.

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Figure 1: Bubble plot of miRNAs that are up- or downregulated in several diseases.
Figure 2: Representative example for the physical proximity of a significantly deregulated miRNA and a known SNP.

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Gene Expression Omnibus

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Acknowledgements

We thank F. Flachsbart, B. Noack and B. Loos for support. This work was financially supported by the German Ministry of Research Education (Bundesministerium für Bildung und Forschung 01EX0806), Hedwig Stalter Foundation, Homburger Forschungsförderungsprogramm and by the Deutsche Forschungsgemeinschaft (LE2783/1-1). Infrastructure support was received from the Deutsche Forschungsgemeinschaft cluster of excellence 'Inflammation at Interfaces'.

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Author notes

  1. Andreas Keller, Petra Leidinger, Andre Franke and Eckart Meese: These authors contributed equally to this work.

Authors and Affiliations

  1. Biomarker Discovery Center, Heidelberg, Germany

    Andreas Keller

  2. Institute of Human Genetics, Saarland University, Medical Faculty, Homburg, Germany

    Andreas Keller, Petra Leidinger, Christina Backes & Eckart Meese

  3. German Cancer Research Center, Functional Genome Analysis, Heidelberg, Germany

    Andrea Bauer & Joerg D Hoheisel

  4. Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany

    Abdou ElSharawy, Gunnar Jacobs, Philip Rosenstiel, Arne Schaefer, Almut Nebel, Sylvia Hofmann, Stefan Schreiber & Andre Franke

  5. Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany

    Jan Haas, Britta Vogel, Hugo A Katus, Wolfgang Rottbauer & Benjamin Meder

  6. febit group, Heidelberg, Germany

    Anke Wendschlag, Peer Staehler, Ioannis Amarantos, Valesca Boisguerin, Cord Staehler, Markus Beier & Matthias Scheffler

  7. Department of General Surgery, University of Heidelberg, Heidelberg, Germany

    Nathalia Giese, Christine Tjaden, Katja Ott, Jens Werner, Thilo Hackert & Markus W Büchler

  8. Department of Neurology, Charité University Hospital, Berlin, Germany

    Klemens Ruprecht

  9. Department of Cardiothoracic Surgery, Voelklingen Heart Center, Voelklingen, Germany

    Hanno Huwer

  10. Department of Pneumology, Voelklingen Lung Center, Voelklingen, Germany

    Junko Huebers

  11. Department of Periodontology, Operative and Preventive Dentistry, University Hospital Bonn, Bonn, Germany

    Henrik Dommisch

  12. Department of Pneumology, University Hospital Medical Center, Freiburg, Germany

    Joachim Müller-Quernheim

  13. Department of Urology, University Clinic, Friedrich-Alexander University, Erlangen-Nuremberg, Nuremberg, Germany

    Bernd Wullich & Bastian Keck

  14. Department of Pediatric Hematology and Oncology, Saarland University, Medical Faculty, Homburg, Germany

    Norbert Graf

  15. Clinic for Dermatology, Venerology and Allergology, Saarland University, Medical Faculty, Homburg, Germany

    Joerg Reichrath

  16. Praxis für Dermatologie, Sulzbach, Germany

    Sven U Jager

  17. Department of Obstetrics and Gynecology, Medical School, University of Wuerzburg, Wuerzburg, Germany

    Joerg Wischhusen, Sebastian F M Haeusler & Johannes Dietl

  18. Interdisciplinary Center for Clinical Research, Junior Research Group 'Tumor progression and immune escape', Medical School, University of Wuerzburg, Wuerzburg, Germany

    Joerg Wischhusen

  19. Center For Bioinformatics, Saarland University, Saarbruecken, Germany

    Hans-Peter Lenhof

  20. First Medical Department, University Clinic Schleswig-Holstein, Kiel, Germany

    Stefan Schreiber

Authors
  1. Andreas Keller
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  2. Petra Leidinger
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  3. Andrea Bauer
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  4. Abdou ElSharawy
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  5. Jan Haas
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  6. Christina Backes
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  7. Anke Wendschlag
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  8. Nathalia Giese
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  9. Christine Tjaden
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  10. Katja Ott
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  11. Jens Werner
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  12. Thilo Hackert
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  13. Klemens Ruprecht
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  14. Hanno Huwer
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  15. Junko Huebers
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  16. Gunnar Jacobs
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  17. Philip Rosenstiel
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  18. Henrik Dommisch
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  19. Arne Schaefer
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  20. Joachim Müller-Quernheim
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  21. Bernd Wullich
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  22. Bastian Keck
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  23. Norbert Graf
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  24. Joerg Reichrath
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  25. Britta Vogel
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  26. Almut Nebel
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  27. Sven U Jager
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  28. Peer Staehler
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  29. Ioannis Amarantos
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  30. Valesca Boisguerin
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  31. Cord Staehler
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  32. Markus Beier
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  33. Matthias Scheffler
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  34. Markus W Büchler
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  35. Joerg Wischhusen
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  36. Sebastian F M Haeusler
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  37. Johannes Dietl
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  38. Sylvia Hofmann
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  39. Hans-Peter Lenhof
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  40. Stefan Schreiber
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  41. Hugo A Katus
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  42. Wolfgang Rottbauer
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  43. Benjamin Meder
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  44. Joerg D Hoheisel
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  45. Andre Franke
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  46. Eckart Meese
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Contributions

A.K. initiated the study; E.M., P.R., J.M-Q., A.B., P.S., V.B., C.S., M.B., M.W.B., J.W., S.F.M.H., J.D., S.S., H.A.K., W.R., B.M., J.D.H. and A.F. designed the study; A.K., P.L., A.E., H.A.K., W.R., B.M., J.D.H., A.F., E.M., S.S. and B.V. wrote the manuscript; A.K., J.H., C.B., A.W., I.A., B.V. and H-P.L. analyzed data; P.L., A.B., C.T., A.E., N.G., K.O., J.W., T.H., G.J., H.D., A.S., B.W., B.K., N.G., A.N., V.B., B.V., S.H. and B.M. performed experiments; C.T., K.O., T.H., K.R., H.H., J.H., G.J., H.D., A.S., B.W., B.K., J.R., S.U.J., N.G., M.S., M.W.B., J.W. and S.F.M.H. collected samples.

Corresponding author

Correspondence to Andreas Keller.

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Competing interests

A.K., C.B., A.W., I.A., P.S., V.B., C.S., M.B., MS have been affiliated with febit, a biotech company specializing in microarray screening.

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Supplementary Figures 1–6, Supplementary Tables 1–8 (PDF 5051 kb)

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Keller, A., Leidinger, P., Bauer, A. et al. Toward the blood-borne miRNome of human diseases. Nat Methods 8, 841–843 (2011). https://doi.org/10.1038/nmeth.1682

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