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

Survivin is a member of the inhibitor of apoptosis protein family. Survivin has splice variants with different biological functions associated with tumorigenesis. We investigated 134 non-small cell lung cancers (NSCLCs) to study the clinical significance of wild-type survivin, survivin-2B, and survivin-deltaEx3. Real-time PCR analyses were performed for their gene expressions. The subcellular localisation of survivin proteins was evaluated by immunohistochemistry. The Ki-67 proliferation index and the apoptotic index were also evaluated. The survivin-deltaEx3 gene expression was significantly higher in stage II–III than in stage I (P=0.0174), and significantly correlated with the nuclear pan-survivin expression (P<0.0001). The Ki-67 index was significantly higher in wild-type survivin-positive tumours (P<0.0001), survivin-deltaEx3-positive tumours (P<0.0001), and tumours with positive expression of the nuclear pan-survivin (P=0.0047). In contrast, the apoptotic index was significantly lower only in wild-type survivin-positive tumours (P<0.0001). Thus, the wild-type survivin gene expression was associated with apoptotic inhibition and tumour proliferation. Furthermore, the survivin-deltaEx3 gene expression was strongly associated with tumour proliferation, especially in advanced stage NSCLCs. In contrast, the survivin-2B gene expression did not correlate with tumour proliferation or tumour apoptosis.