BACKGROUND: KRAB-associated protein 1 (KAP1) is a universal corepressor for Kruppel-associated box zinc finger proteins. Here we demonstrate the biological function and clinical significance of KAP1 expression in gastric cancer. METHODS: Knockdown of the KAP1 gene by siRNA transfection was performed to evaluate KAP1 function in gastric cancer cells. Real-time polymerase chain reaction was performed in 91 samples obtained from gastric cancer patients. RESULTS: The proliferation rate was impaired and resistance to anoikis was decreased after knockdown of KAP1 in the gastric cancer cell lines AZ521 and KATO III. Expression of the KAP1 gene was significantly higher in cancerous tissues than in noncancerous tissues (P < .05). Patients with high KAP1 expression showed a higher incidence of peritoneal carcinomatosis (P < .05) and significantly poorer overall survival compared to patients with low KAP1 expression (5-year overall survival rates, 35.4% and 50.5%, respectively; P < .05). Multivariate analysis revealed that high KAP1 expression was an independent prognostic factor (risk ratio, 1.44; 95% confidence interval, 1.03-1.99; P < .05). Intriguingly, high KAP1 expression was also an independent factor for peritoneal carcinomatosis (odds ratio, 4.53; 95% confidence interval, 1.27-18.5; P < .05). CONCLUSIONS: KAP1 provides a survival advantage to gastric cancer cells and is an independent factor for peritoneal dissemination in patients with gastric cancer. These results suggest that KAP1 plays an important role in progression to peritoneal carcinomatosis in gastric cancer patients.
BACKGROUND:KRAB-associated protein 1 (KAP1) is a universal corepressor for Kruppel-associated box zinc finger proteins. Here we demonstrate the biological function and clinical significance of KAP1 expression in gastric cancer. METHODS: Knockdown of the KAP1 gene by siRNA transfection was performed to evaluate KAP1 function in gastric cancer cells. Real-time polymerase chain reaction was performed in 91 samples obtained from gastric cancerpatients. RESULTS: The proliferation rate was impaired and resistance to anoikis was decreased after knockdown of KAP1 in the gastric cancer cell lines AZ521 and KATO III. Expression of the KAP1 gene was significantly higher in cancerous tissues than in noncancerous tissues (P < .05). Patients with high KAP1 expression showed a higher incidence of peritoneal carcinomatosis (P < .05) and significantly poorer overall survival compared to patients with low KAP1 expression (5-year overall survival rates, 35.4% and 50.5%, respectively; P < .05). Multivariate analysis revealed that high KAP1 expression was an independent prognostic factor (risk ratio, 1.44; 95% confidence interval, 1.03-1.99; P < .05). Intriguingly, high KAP1 expression was also an independent factor for peritoneal carcinomatosis (odds ratio, 4.53; 95% confidence interval, 1.27-18.5; P < .05). CONCLUSIONS:KAP1 provides a survival advantage to gastric cancer cells and is an independent factor for peritoneal dissemination in patients with gastric cancer. These results suggest that KAP1 plays an important role in progression to peritoneal carcinomatosis in gastric cancerpatients.
Authors: Lu Chen; Dung-Tsa Chen; Courtney Kurtyka; Bhupendra Rawal; William J Fulp; Eric B Haura; W Douglas Cress Journal: J Biol Chem Date: 2012-10-11 Impact factor: 5.157