Prognostic significance of x-linked inhibitor of apoptosis protein expression in renal cell carcinoma

Abstract

5105 Background: X-linked inhibitor of apoptosis protein ( XIAP ) is one of the IAP family members which block apoptosis through inhibition of caspase 3 and 9. However, little is known about the clinical significance of XIAP in a variety of cancers including renal cell carcinoma ( RCC ). The current study investigated XIAP expression in 120 normal kidneys and RCCs and examined its prognostic significance. Methods: The level of XIAP expression was determined by Western blot analysis using 120 non-fixed fresh frozen tissues of RCCs and normal kidneys. Cytotoxicity was examined by the MTT assay. Results: The mean level of XIAP expression was 1.6-fold higher in RCC compared to autologous normal kidney. In Stage I/II RCC, the mean XIAP expression level was almost identical to that in normal kidney, whereas XIAP expression in Stage III/IV RCC was 2.5-fold higher. The level of XIAP expression positively correlated with the grade of RCC. Patients with RCC with low XIAP expression had a longer postoperative disease-specific survival than those with high expression in the 5-year follow-up. Treatment of RCC cells with XIAP antisense oligonucleotide enhanced tumor necrosis factor ( TNF )-α- mediated, Fas-mediated and TNF-related apoptosis-inducing ligand ( TRAIL )-mediated apoptosis. Conclusions: The present study has demonstrated that XIAP expression was up-regulated in RCC, and that high XIAP expression in RCC predicted worse prognosis. In addition, XIAP antisense oligonucleotide sensitized RCC to TNF-α-induced, Fas-induced and TRAIL-induced apoptosis. These findings suggest that XIAP expression in RCC may be used as a prognostic parameter, and that down-regulation of XIAP expression in RCC may potentiate immunotherapy. No significant financial relationships to disclose.