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Disturbed XIAP and XAF1 expression balance is an independent prognostic factor in gastric adenocarcinomas
Tomotaka Shibata1, Tsuyoshi Noguchi, Shinsuke Takeno
1Department of Oncological Science Surgery II, Faculty of Medicine, Oita University, Yufu City, Oita, Japan. shiba@med.oita-u.ac.jp
Background:
Dysregulation of apoptosis is a key factor in carcinogenesis and tumor progression. X-linked inhibitor of apoptosis (XIAP) is the most potent member of the inhibitor of apoptosis protein (IAP) family, which directly inhibits apoptosis by binding to caspases. Antagonists of XIAP have recently been identified: second mitochondria-derived activator of caspase/direct IAP-binding protein with low PI (Smac/DIABLO) and XIAP-associated factor 1 (XAF1). However, little research has been conducted on the association between gastric cancer survival and the mechanism of apoptosis involving XIAP and its antagonists, Smac/DIABLO and XAF1.
Methods:
XIAP, Smac/DIABLO, and XAF1 expression was analyzed by immunohistochemistry (IHC) in 187 gastric adenocarcinomas. Correlations between XIAP, Smac/DIABLO or XAF1 expression and clinicopathological factors were analyzed. Disease-specific survival after surgery was examined.
Results:
Of 187 samples, XIAP was overexpressed in 140, Smac was overexpressed in 117, and XAF1 was overexpressed in 106. Individually, XIAP, Smac, and XAF1 were not significantly associated with disease-specific survival. However, patients showing high expression of XIAP and low expression of XAF1 had significantly poorer survival when compared with other groups (P = 0.024).
Conclusion:
The expression balance of XIAP and XAF1 is an independent prognostic factor in gastric adenocarcinoma.
Insights
The balance between X-linked inhibitor of apoptosis (XIAP) and XIAP-associated factor 1 (XAF1) expression predicts gastric cancer survival. High XIAP with low XAF1 indicates poorer outcomes in gastric adenocarcinoma patients.
Area of Science:
- Oncology
- Cell Biology
- Molecular Pathology
Background:
- Apoptosis dysregulation is crucial in cancer development and progression.
- X-linked inhibitor of apoptosis (XIAP) inhibits apoptosis by binding caspases.
- Second mitochondria-derived activator of caspase/direct IAP-binding protein with low PI (Smac/DIABLO) and XIAP-associated factor 1 (XAF1) are XIAP antagonists.
Purpose of the Study:
- To investigate the association between gastric cancer survival and the expression of XIAP and its antagonists, Smac/DIABLO and XAF1.
- To determine if XIAP, Smac/DIABLO, or XAF1 expression levels correlate with gastric adenocarcinoma prognosis.
Main Methods:
- Immunohistochemistry (IHC) was used to analyze XIAP, Smac/DIABLO, and XAF1 expression in 187 gastric adenocarcinomas.
- Correlations between protein expression and clinicopathological factors were examined.
- Disease-specific survival rates after surgery were analyzed.
Main Results:
- XIAP overexpression was observed in 140 samples, Smac in 117, and XAF1 in 106.
- Individual expression of XIAP, Smac, or XAF1 did not significantly correlate with disease-specific survival.
- A significant association with poorer survival was found in patients with high XIAP and low XAF1 expression (P = 0.024).
Conclusions:
- The relative expression levels of XIAP and XAF1 serve as an independent prognostic marker for gastric adenocarcinoma.
- The balance between XIAP and XAF1 is critical for predicting patient outcomes.
