KAP1 is associated with peritoneal carcinomatosis in gastric cancer.
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.
Yokoe
Takeshi
T
Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan. takesche@clin.medic.mie-u.ac.jp
Toiyama
Yuji
Y
Okugawa
Yoshinaga
Y
Tanaka
Koji
K
Ohi
Masaki
M
Inoue
Yasuhiro
Y
Mohri
Yasuhiko
Y
Miki
Chikao
C
Kusunoki
Masato
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000076183:Tripartite Motif-Containing Protein 28; D055815:Young Adult
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28