Although it was observed that inhibition of the antiapoptotic protein survivin expression in lung cancer cells induces apoptosis, the expression and function of survivin variants, survivin-2B and survivin-deltaEx3 in lung cancer have not yet been characterized. To study the potential prognostic/diagnostic role of survivin-2B and survivin-deltaEx3 in non-small cell lung cancer (NSCLC), we analyzed 24 NSCLC samples by semi-quantitative RT-PCR. Surprisingly, our results revealed that high-level expression of survivin-2B is significantly associated with the patient category of “no relapse & alive”. In contrast, high-level expression of survivin-deltaEx3 is highly associated with the patient category of “relapse & dead”. Consistent with this observation, plasmid-mediated expression of survivin-2B in A549 lung cancer cells disrupted the mitochondria potential, while expression of survivin-deltaEx3 protected the mitochondria potential. These findings, for the first time, provided evidence that survivin-2B and survivin-deltaEx3 play opposite roles in disease relapse and patient survival in NSCLC, which likely employs a mechanism to differentially affect mitochondria potential/cell viability. Thus, controlling the expression of survivin-2B and survivin-deltaEx3 may represent novel approaches for cancer therapeutics in NSCLC.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]