title: miRNAs can be generally associated with human pathologies as exemplified for miR-144.
abstract: BACKGROUND
  miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists.
  
  
  METHODS
  We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR.
  
  
  RESULTS
  We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 (95% CI: 0.703-0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait.
  
  
  CONCLUSIONS
  Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers.
authors.affiliation: Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany. ack@bioinf.uni-sb.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
authors.affiliation: Institute of Human Genetics, Saarland University, Homburg, Germany. p.leidinger@mx.uni-saarland.de.
authors.forename: Petra
authors.initials: P
authors.lastname: Leidinger
authors.affiliation: Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany. britta.vogel@med.uni-heidelberg.de.
authors.forename: Britta
authors.initials: B
authors.lastname: Vogel
authors.affiliation: Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany. c.backes@mx.uni-saarland.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Backes
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, Germany. a.sharawy@ikmb.uni-kiel.de.
authors.forename: Abdou
authors.initials: A
authors.lastname: ElSharawy
authors.affiliation: Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany. valentina.galata@gmail.com.
authors.forename: Valentina
authors.initials: V
authors.lastname: Galata
authors.affiliation: Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany. sabine.mueller@uniklinikum-saarland.de.
authors.forename: Sabine C
authors.initials: SC
authors.lastname: Mueller
authors.affiliation: Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany. sabine.marquart@med.uni-heidelberg.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Marquart
authors.affiliation: Department of Gynecology and Obstetrics, University Breast Center Franconia, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. michael.schrauder@uk-erlangen.de.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Schrauder
authors.affiliation: Department of Gynecology and Obstetrics, University Breast Center Franconia, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. reiner.strick@uk-erlangen.de.
authors.forename: Reiner
authors.initials: R
authors.lastname: Strick
authors.affiliation: German Cancer Research Center, Heidelberg, Germany. andrea.bauer@dkfz.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bauer
authors.affiliation: University Hospital Würzburg, Würzburg, Germany. wischhusen_J@ukw.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Wischhusen
authors.affiliation: Comprehensive Biomarker Center, Heidelberg, Germany. markus.beier@cbioc.com.
authors.forename: Markus
authors.initials: M
authors.lastname: Beier
authors.affiliation: Comprehensive Biomarker Center, Heidelberg, Germany. jochen.kohlhaas@cbioc.com.
authors.forename: Jochen
authors.initials: J
authors.lastname: Kohlhaas
authors.affiliation: Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany. hugo.katus@med.uni-heidelberg.de.|German Center for Cardiovascular Research - DZHK, Germany, Heidelberg. hugo.katus@med.uni-heidelberg.de.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: German Cancer Research Center, Heidelberg, Germany. j.hoheisel@dkfz.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hoheisel
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, Germany. a.franke@ikmb.uni-kiel.de.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.affiliation: Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany. benjamin.meder@med.uni-heidelberg.de.|German Center for Cardiovascular Research - DZHK, Germany, Heidelberg. benjamin.meder@med.uni-heidelberg.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Meder
authors.affiliation: Institute of Human Genetics, Saarland University, Homburg, Germany. hgemee@uniklinik-saarland.de.
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C554293:MIRN144 microRNA, human; D035683:MicroRNAs