title: Prognostic impact of mRNA levels of osteopontin splice variants in soft tissue sarcoma patients.
abstract: BACKGROUND
  It is well known that osteopontin (OPN) plays an important role in tumor progression and that a high OPN expression level in several tumor entities correlates with poor prognosis in cancer patients. However, little is known about the prognostic relevance of the OPN mRNA splice variants.
  
  
  METHODS
  We analyzed the mRNA expression levels of different OPN splice variants in tumor tissue of 124 soft tissue sarcoma (STS) patients. Quantitative real-time PCR (qRT-PCR) was used to analyze the mRNA expression level of three OPN splice variants (OPN-a, -b and -c).
  
  
  RESULTS
  The multivariate Cox's proportional hazard regression model revealed that high mRNA expression levels of OPN splice variants are significantly associated with poor prognosis in STS patients (n = 124). Women (n = 68) with high mRNA expression levels of OPN-a and OPN-b have an especially elevated risk of tumor-related death (OPN-a: RR = 3.0, P = 0.01, CI = 1.3-6.8; OPN-b: RR = 3.4, P = 0.01, CI = 1.4-8.2). In particular, we found that high mRNA expression levels of OPN-b and OPN-c correlated with a high risk of tumor-related death in STS patients that received radiotherapy (n = 52; OPN-b: RR = 10.3, P < 0.01, CI = 2.0-53.7; OPN-c: RR = 11.4, P < 0.01, CI = 2.2-59.3).
  
  
  CONCLUSIONS
  Our study shows that elevated mRNA expression levels of OPN splice variants are negative prognostic and predictive markers for STS patients. Further studies are needed to clarify the impact of the OPN splice variants on prognosis.
authors.affiliation: Department of Radiotherapy, Martin-Luther-University of Halle-Wittenberg, Saale, Germany. antje.hahnel@medizin.uni-halle.de
authors.forename: Antje
authors.initials: A
authors.lastname: Hahnel
authors.forename: Henri
authors.initials: H
authors.lastname: Wichmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Greither
authors.forename: Matthias
authors.initials: M
authors.lastname: Kappler
authors.forename: Peter
authors.initials: P
authors.lastname: Würl
authors.forename: Matthias
authors.initials: M
authors.lastname: Kotzsch
authors.forename: Helge
authors.initials: H
authors.lastname: Taubert
authors.forename: Dirk
authors.initials: D
authors.lastname: Vordermark
authors.forename: Matthias
authors.initials: M
authors.lastname: Bache
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012509:Sarcoma / Q000175:diagnosis / Q000235:genetics*; D012983:Soft Tissue Neoplasms / Q000175:diagnosis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D053495:Osteopontin