Elevated expression of survivin-splice variants predicts a poor outcome for soft-tissue sarcomas patients

Abstract

The aim of this study was to investigate the level and the prognostic value of the expression of different survivin transcript variants -survivin, survivin-DEx3 and survivin-2B -in tumours of 76 soft tissue sarcoma (STS) patients. The expression of survivin transcript variants in STS tissue samples and in 12 nonmalignant control tissues was analysed by quantitative RT-PCRs. Expression levels of all survivin transcript variants were strongly elevated in STS compared to normal tissues. A positive correlation between expression of splice variants and tumour stage was found (P ¼ 0.02; v 2 test). The multivariate Cox's proportional hazards regression model revealed a 7.3-fold increased risk of tumour-related death for patients with survivin-DEx3 overexpressing tumours (P ¼ 0.007). The effect of surivivin (wildtype variant) and survivin-2B was less pronounced but still significant (2.2-and 1.9-fold, resp., Po0.05 each). Our results show for the first time that mRNA expression of survivin-variants is significantly correlated to a poor prognosis for STS patients, and we suggest expression of survivin splice variants together with tumour stage as independent predictor of survival.

The clinical significance of splice variants and subcellular localisation of survivin in non-small cell lung cancers

“…In fact, previous clinical studies also revealed the survivindeltaEx3 expression to be associated with a high proliferation rate (Takashima et al, 2005). Recent studies have revealed that the survivin-deltaEx3 overexpression is a significant poor prognostic factor in cancer patients, including NSCLCs (Ling et al, 2005;Taubert et al, 2005). Furthermore, the present study found the survivin-deltaEx3 gene expression to be significantly higher in advanced-stage NSCLCs.…”

“…Previous clinical studies have reported the survivin expression to be associated with tumour cell proliferation, apoptotic inhibition, and a poor prognosis in various human cancers, including NSCLCs (Martinez et al, 2004;Shinohara et al, 2005). However, only a few clinical reports studied these splice variants of survivin in human cancers (Mahotka et al, 2002a;Meng et al, 2004;Ling et al, 2005;Taubert et al, 2005). Therefore, to clarify the clinical significance of these splice variants of survivin in NSCLCs, we performed the present study on the gene expressions of wild-type survivin, survivin-2B, and survivin-deltaEx3 in relation to the subcellular localisation of survivin proteins, tumour cell proliferation, and apoptosis.…”

Characterisation of the anti-apoptotic function of survivin-ΔEx3 during TNFα−mediated cell death

“…In addition, expression of survivin and survivin-DEx3 remains constant in different stages of cancer (Krieg et al, 2002). Patients with soft-tissue sarcoma also have an increased risk of tumour-related death when survivin-DEx3 is overexpressed (Taubert et al, 2005). The expression level of survivin-DEx3 is inversely correlated with apoptotic index in gastric cancers (Meng et al, 2004).…”

The effects of knockdown of wild-type survivin, survivin-2B or survivin-Δ3 on the radiosensitization in a soft tissue sarcoma cells in vitro under different oxygen conditions

“…In a previous study on soft tissue sarcoma, patients with survivin-D3 overexpressing tumors had a sevenfold increased risk of tumor-related death in a multivariate Cox's proportional hazards regression model. 37 This implied that not only wild-type survivin, but also the survivin isoforms, for example, survivin-D3…”

“…Patients with soft tissue sarcoma whose tumors overexpressed survivin-D3 had a sevenfold increased risk of tumor-related death. 37 Recently, it has been found that tumor-specific expression of survivin is increased by hypoxia, and the addition of hypoxia-responsive elements to the survivin promoter results in a further increase in its expression. 38 It seems that survivin expression is dependent and independent of the most prominent factors of hypoxia and angiogenesis Hif-1a and VEGF, respectively.…”