Disturbed XIAP and XAF1 expression balance is an independent prognostic factor in gastric adenocarcinomas.
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).


CONCLUSIONS
The expression balance of XIAP and XAF1 is an independent prognostic factor in gastric adenocarcinoma.
Shibata
Tomotaka
T
Department of Oncological Science Surgery II, Faculty of Medicine, Oita University, Yufu City, Oita, Japan. shiba@med.oita-u.ac.jp
Noguchi
Tsuyoshi
T
Takeno
Shinsuke
S
Gabbert
Helmut E
HE
Ramp
Uwe
U
Kawahara
Katsunobu
K
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*; D016335:Zinc Fingers
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C417551:XAF1 protein, human; C496866:XIAP protein, human