title: Combined mRNA expression levels of members of the urokinase plasminogen activator (uPA) system correlate with disease-associated survival of soft-tissue sarcoma patients.
abstract: BACKGROUND
  Members of the urokinase-type plasminogen activator (uPA) system are up-regulated in various solid malignant tumors. High antigen levels of uPA, its inhibitor PAI-1 and its receptor uPAR have recently been shown to be associated with poor prognosis in soft-tissue sarcoma (STS) patients. However, the mRNA expression of uPA system components has not yet been comprehensively investigated in STS patients.
  
  
  METHODS
  The mRNA expression level of uPA, PAI-1, uPAR and an uPAR splice variant, uPAR-del4/5, was analyzed in tumor tissue from 78 STS patients by quantitative PCR.
  
  
  RESULTS
  Elevated mRNA expression levels of PAI-1 and uPAR-del4/5 were significantly associated with clinical parameters such as histological subtype (P = 0.037 and P < 0.001, respectively) and higher tumor grade (P = 0.017 and P = 0.003, respectively). In addition, high uPAR-del4/5 mRNA values were significantly related to higher tumor stage of STS patients (P = 0.031). On the other hand, mRNA expression of uPA system components was not significantly associated with patients' survival. However, in STS patients with complete tumor resection (R0), high PAI-1 and uPAR-del4/5 mRNA levels were associated with a distinctly increased risk of tumor-related death (RR = 6.55, P = 0.054 and RR = 6.00, P = 0.088, respectively). Strikingly, R0 patients with both high PAI-1 and uPAR-del4/5 mRNA expression levels showed a significant, 19-fold increased risk of tumor-related death (P = 0.044) compared to the low expression group.
  
  
  CONCLUSIONS
  Our results suggest that PAI-1 and uPAR-del4/5 mRNA levels may add prognostic information in STS patients with R0 status and distinguish a subgroup of R0 patients with low PAI-1 and/or low uPAR-del4/5 values who have a better outcome compared to patients with high marker levels.
authors.affiliation: Institute of Pathology, Dresden University of Technology, Dresden, Germany. matthias.kotzsch@uniklinikum-dresden.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Kotzsch
authors.forename: Viktor
authors.initials: V
authors.lastname: Magdolen
authors.forename: Thomas
authors.initials: T
authors.lastname: Greither
authors.forename: Matthias
authors.initials: M
authors.lastname: Kappler
authors.forename: Matthias
authors.initials: M
authors.lastname: Bache
authors.forename: Christine
authors.initials: C
authors.lastname: Lautenschläger
authors.forename: Susanne
authors.initials: S
authors.lastname: Füssel
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Eckert
authors.forename: Thomas
authors.initials: T
authors.lastname: Luther
authors.forename: Gustavo
authors.initials: G
authors.lastname: Baretton
authors.forename: Peter
authors.initials: P
authors.lastname: Würl
authors.forename: Helge
authors.initials: H
authors.lastname: Taubert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000706:statistics & numerical data; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*; D055815:Young Adult
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D020033:Protein Isoforms; D012333:RNA, Messenger; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator