title: Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma.
abstract: BACKGROUND
  Improved detection methods for diagnosis of malignant pleural mesothelioma (MPM) are essential for early and reliable detection as well as treatment. Since recent data point to abnormal levels of microRNAs (miRNAs) in tumors, we hypothesized that a profile of deregulated miRNAs may be a marker of MPM and that the levels of specific miRNAs may be used for monitoring its progress.
  
  
  RESULTS
  miRNAs isolated from fresh-frozen biopsies of MPM patients were tested for the expression of 88 types of miRNA involved in cancerogenesis. Most of the tested miRNAs were downregulated in the malignant tissues compared with the normal tissues. Of eight significantly downregulated, three miRNAs were assayed in cancerous tissue and adjacent non-cancerous tissue sample pairs collected from 27 formalin-fixed, paraffin-embedded MPM tissues by quantitative RT-PCR. Among the miRNAs tested, only miR-126 significantly remained downregulated in the malignant tissues. Furthermore, the performance of the selected miR-126 as biomarker was evaluated in serum samples of asbestos-exposed subjects and MPM patients and compared with controls. MiR-126 was not affected by asbestos exposure, whereas it was found strongly associated with VEGF serum levels. Levels of miR-126 in serum, and its levels in patients' serum in association with a specific marker of MPM, SMRPs, correlate with subjects at high risk to develop MPM.
  
  
  CONCLUSIONS
  We propose miR-126, in association with SMRPs, as a marker for early detection of MPM. The identification of tumor biomarkers used alone or, in particular, in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos.
authors.affiliation: Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Lory
authors.initials: L
authors.lastname: Santarelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Strafella
authors.forename: Sara
authors.initials: S
authors.lastname: Staffolani
authors.forename: Monica
authors.initials: M
authors.lastname: Amati
authors.forename: Monica
authors.initials: M
authors.lastname: Emanuelli
authors.forename: Davide
authors.initials: D
authors.lastname: Sartini
authors.forename: Valentina
authors.initials: V
authors.lastname: Pozzi
authors.forename: Damiano
authors.initials: D
authors.lastname: Carbonari
authors.forename: Massimo
authors.initials: M
authors.lastname: Bracci
authors.forename: Elettra
authors.initials: E
authors.lastname: Pignotti
authors.forename: Paola
authors.initials: P
authors.lastname: Mazzanti
authors.forename: Armando
authors.initials: A
authors.lastname: Sabbatini
authors.forename: Renzo
authors.initials: R
authors.lastname: Ranaldi
authors.forename: Stefano
authors.initials: S
authors.lastname: Gasparini
authors.forename: Jiri
authors.initials: J
authors.lastname: Neuzil
authors.forename: Marco
authors.initials: M
authors.lastname: Tomasetti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001194:Asbestos / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D015536:Down-Regulation / Q000187:drug effects; D055088:Early Detection of Cancer; D004781:Environmental Exposure / Q000009:adverse effects; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000737:chemistry* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012995:Solubility
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D010455:Peptides; D001194:Asbestos; D000090204:Mesothelin