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

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).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).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.Osteopontin is a secreted phosphoprotein that plays an important role in tumor progression. It affects processes such as cellular growth, cell migration, invasion, metastasis and decay of the extracellular matrix [1]. Several studies showed that an increased OPN expression correlates with poor prognosis in cancer patients [2-4]. However, only a few studies have analyzed the importance of OPN for tumor progression in sarcomas. OPN protein expression level was shown to be elevated in tumor cells, and high OPN levels were associated with high tumor stage, tumor grade and poor survival in sarcoma patients [5-7]. Additionally, Bramwell et al. (2005) showed that OPN mRNA is also overexpressed in the tumor tissue of STS patients. In a previous study, we demonstrated that higher OPN protein expression levels in tumor tissue and ser