Differential Expression of Survivin and Its Splice Variants, Survivin-DeltaEx3 and Survivin-2B, in Bladder Cancer

Background: Survivin, an inhibitor of apoptosis protein (IAP), has been regarded as a valuable tumor marker for diagnosis and prognosis of bladder cancer. Recently, three splice variants of the gene with different anti-apoptotic activities have been reported. However, there is no data on the expression and potential causative roles of these transcripts in bladder cancer. Here, we have investigated the expression pattern of survivin and two of its splice variants, survivin-DeltaEx3 and survivin-2B, in malignant versus non-malignant bladder tissues.

Methods: We used semi-quantitative RT-PCR analysis to examine the expression of survivin variants in 30 transitional cell carcinoma, 19 matched non-tumor, and 9 apparently healthy control tissue samples of the bladder. DNA sequencing was used to confirm the identity of amplified fragments.

Results: For all examined samples, survivin was the predominant transcript, being present in 83% of tumor and 25% of non-tumor bladder tissue samples, and survivin-2B was the least detected isoform. The expression levels of survivin and survivin-DeltaEx3 was significantly higher in neoplastic compared to non-neoplastic tissues (P<0.001) and both the sensitivity and specificity of survivin were superior to survivin-DeltaEx3 (83% and 75% for survivin and 76% and 64% for survivin-DeltaEx3, respectively). Also, the expression levels of survivin and survivin-DeltaEx3 showed a significant correlation (P=0.02) with tumor invasiveness (pT1/pTa).

Conclusion: Our data revealed for the first time a differential expression pattern of survivin splice variants in bladder tissues, which potentially could have a practical usefulness in diagnosis and/or therapy of the tumor.