Abstract
BackgroundIt 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.MethodsWe 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).ResultsThe 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).ConclusionOur 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.
Highlights
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
Our study shows that elevated mRNA expression levels of OPN splice variants are negative prognostic and predictive markers for soft tissue sarcoma (STS) patients
Several studies showed that OPN-c is expressed at higher levels in invasive tumor cells compared to noninvasive tumor cells [13,14,17,21]. It has been demonstrated in these studies that OPN-c influences the expression of several migration/invasion markers, such as MMP-2, MMP-9 and uPA, which promote tumor cell invasion. This is in accordance with the correlation we found between the OPN splice variants, the uPA, uPAR
Summary
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. 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 [2,3,4]. 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 [5,6,7].
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