title: Low tissue levels of miR-125b predict malignancy in solitary fibrous tumors of the pleura.
abstract: Solitary fibrous tumors of the pleura (SFTP) are rare neoplasia of the chest. A subset of SFTP follows a malignant course, sometimes several years after complete resection. Traditional scoring systems based on clinical and histological features are poor predictors of biological behavior. This study aimed to investigate tumor-associated miRNAs expression as novel biomarkers to predict the clinical behavior of SFTP.
  
  
  
  Formalin-fixed and paraffin-embedded SFTP tissues blocks from patients surgically resected between 1992 and 2013 at two tertiary care teaching hospitals were included. SFTP tumors were categorized as either malignant or benign variants according to the WHO classification. Following miRNAs levels were measured: let-7a, miR-16b, miR-17, miR-21, miR-31, miR-34a, miR-92a, miR-125a, miR-125b, miR-195-5b, miR-203a, and miR-223. Differential gene expressions which were calculated with the threshold cycle (Ct) method were compared among the two variants.
  
  
  
  Thirty-eight patients (40% male, mean age 62.2 (±10.9) years) were included. Expression levels of miR-125b showed a significant difference between benign compared to malignant variants (-3.08 ± 0.93 vs. -2.22 ± 1.36, p = 0.0068). Furthermore, lower levels of miR-125b were found to be associated with increased tumor size (p = 0.0414). Thus, downregulation of miR-125b indicates malignant transformation. All other investigated miRNAs were not associated with grading of SFTP.
  
  
  
  Our data suggest a potential role of miR-125b in the pathogenesis of tumor growth and malignant transformation of SFTP, respectively. Further studies have to address the potential use of miRNA-125b as a biomarker or therapeutic target in SFTP.
authors.affiliation: Department of Pulmonology, University Hospital Zurich, University of Zurich, Rämistr. 100, 8091, Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Brock
authors.affiliation: Department of Pulmonology, University Hospital Zurich, University of Zurich, Rämistr. 100, 8091, Zurich, Switzerland.
authors.forename: Selma
authors.initials: S
authors.lastname: Hottinger
authors.affiliation: Department of Pulmonology, University Hospital Zurich, University of Zurich, Rämistr. 100, 8091, Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Diebold
authors.affiliation: Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Alex
authors.initials: A
authors.lastname: Soltermann
authors.affiliation: Institute of Pathology, Cantonal Hospital St Gallen, St Gallen, Switzerland.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Jochum
authors.affiliation: Department of Pulmonology, University Hospital Zurich, University of Zurich, Rämistr. 100, 8091, Zurich, Switzerland.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Kohler
authors.affiliation: Department of Pulmonology, University Hospital Zurich, University of Zurich, Rämistr. 100, 8091, Zurich, Switzerland.
authors.forename: Lars C
authors.initials: LC
authors.lastname: Huber
authors.affiliation: Department of Pulmonology, University Hospital Zurich, University of Zurich, Rämistr. 100, 8091, Zurich, Switzerland. daniel.franzen@usz.ch.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Franzen
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D054363:Solitary Fibrous Tumor, Pleural / Q000175:diagnosis* / Q000378:metabolism*; D013557:Switzerland
chemical_list: D014408:Biomarkers, Tumor; C531888:MIRN125 microRNA, human; D035683:MicroRNAs
keywords: Biomarker; Pleura; Solitary fibrous tumor; microRNA