KAP1 Is Associated With Peritoneal Carcinomatosis in Gastric Cancer
KAP1 Is Associated With Peritoneal Carcinomatosis in Gastric Cancer
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DOI：
10.1245/s10434-009-0795-8
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发表时间：
2010-03-01
影响因子：
3.7
通讯作者：
Kusunoki, Masato
中科院分区：
文献类型：
--
作者：
Yokoe, Takeshi;Toiyama, Yuji;Kusunoki, Masato
KRAB相关蛋白1（KAP 1）是Kruppel相关盒锌指蛋白的一种通用辅阻遏物。本研究旨在探讨KAP 1在胃癌中表达的生物学功能及其临床意义，并通过siRNA转染KAP 1基因来研究KAP 1在胃癌细胞中的功能。采用实时荧光定量PCR技术检测91例胃癌患者标本，发现KAP 1基因敲低后，胃癌细胞株AZ 521和KATO III的增殖能力受到抑制，抗失巢凋亡能力下降。KAP 1基因在癌组织中的表达显著高于癌旁组织（P <0.05）。与KAP 1低表达的患者相比，KAP 1高表达的患者腹膜癌转移的发生率更高（P < .05），总生存率明显较差（5年总生存率分别为35.4%和50.5%; P < .05）。多因素分析显示KAP 1高表达是独立的预后因素（危险比，1.44; 95%可信区间，1.03-1.99; P <0.05）。有趣的是，KAP 1高表达也是腹膜癌转移的独立因素（比值比，4.53; 95%置信区间，1.27-18.5; P <0.05）。KAP 1为胃癌细胞提供了生存优势，是胃癌患者腹膜转移的独立因素。这些结果表明，KAP 1在胃癌患者腹膜癌转移的进展中起重要作用。
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.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.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).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.