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Open Access Research article

Prognostic impact of mRNA levels of osteopontin splice variants in soft tissue sarcoma patients

Antje Hahnel1*, Henri Wichmann1, Thomas Greither2, Matthias Kappler3, Peter Würl4, Matthias Kotzsch5, Helge Taubert367, Dirk Vordermark1 and Matthias Bache1

Author Affiliations

1 Department of Radiotherapy, Martin-Luther-University of Halle-Wittenberg, Dryanderstr.4, Halle (Saale) 06110, Germany

2 Centre for Reproductive Medicine and Andrology, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Str. 40, Halle (Saale) 06907, Germany

3 Department of Oral and Maxillofacial Plastic Surgery, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Str. 40, Halle (Saale) 06907, Germany

4 Department of General and Visceral Surgery, Diakoniekrankenhaus, Advokatenweg 1, Halle (Saale) 06114, Germany

5 Institute of Pathology, Dresden University of Technology, Fetscherstr.74, Dresden 01307, Germany

6 Clinic of Urology, FA University Hospital Erlangen, Glückstr. 6, Erlangen 91054, Germany

7 Nikolaus-Fiebiger-Center for Molecular Medicine, FA University Erlangen-Nürnberg, Erlangen-Nürnberg, Germany

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BMC Cancer 2012, 12:131  doi:10.1186/1471-2407-12-131

Published: 2 April 2012

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).

Conclusion

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.