Department of Radiotherapy, Martin-Luther-University of Halle-Wittenberg, Saale, Germany.
BMC Cancer. 2012 Apr 2;12:131. doi: 10.1186/1471-2407-12-131.
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.
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.
众所周知,骨桥蛋白(OPN)在肿瘤进展中起着重要作用,并且几种肿瘤实体中的高 OPN 表达水平与癌症患者的预后不良相关。然而,OPN mRNA 剪接变体的预后相关性知之甚少。
我们分析了 124 名软组织肉瘤(STS)患者肿瘤组织中不同 OPN 剪接变体的 mRNA 表达水平。定量实时 PCR(qRT-PCR)用于分析三种 OPN 剪接变体(OPN-a、-b 和 -c)的 mRNA 表达水平。
多变量 Cox 比例风险回归模型显示,OPN 剪接变体的高 mRNA 表达水平与 STS 患者的预后不良显著相关(n=124)。高 OPN-a 和 OPN-b mRNA 表达水平的女性(n=68)肿瘤相关死亡风险特别高(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)。特别是,我们发现 OPN-b 和 OPN-c 的高 mRNA 表达水平与接受放疗的 STS 患者肿瘤相关死亡风险相关(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)。
我们的研究表明,OPN 剪接变体的高 mRNA 表达水平是 STS 患者的负预后和预测标志物。需要进一步研究来阐明 OPN 剪接变体对预后的影响。