Expression of apoptosis-related proteins and its clinical implication in surgically resected gastric carcinoma

Abstract

Apoptosis, via caspase cascade, is involved in tumorigenesis and progression, and thus, altered apoptosis-related protein expressions have clinical and prognostic significance. Moreover, the apoptosis pathway is highlighted due to the recent introduction of apoptosis-targeted therapy for several genes such as the X-linked inhibitor of apoptosis protein (XIAP). XIAP is the most potent direct inhibitor of caspase, and XIAP-associated factor 1 (XAF1) and secondary mitochondrial activator of caspase/direct IAP-binding protein with low PI (Smac/DIABLO) are negative regulators of XIAP. In this study, we evaluated the expression of these proteins and investigated their clinical and prognostic significance in gastric carcinomas. Immunohistochemical analysis by using the tissue array method was performed for XIAP, survivin, Bcl-2, XAF1, Smac/DIABLO, and cleaved caspase-3 proteins in 1,162 surgically resected gastric carcinoma cases. XIAP expression was related to the advanced stage. The expression of XIAP showed negative relationship with XAF1 and Smac/DIABLO expressions. In addition, XIAP expression was associated with a poor prognosis and was also proved to be an independent prognostic factor. Cleaved caspase-3 expression was related to the early stage. In addition, cleaved caspase-3 expression was associated with a favorable prognosis and was also proved to be an independent prognostic factor. The expression of XIAP showed an inverse relationship with cleaved caspase-3. In addition, the expression of XAF1 and Smac/DIABLO had a positive relationship with cleaved caspase-3. These findings are consistent with their known functions, and they may help to identify individuals best suited for apoptosis-targeted therapy as a baseline data in gastric carcinoma.