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Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e318214bd30
Original Articles: Hepatology and Nutrition

Gene Expression Profiling Reveals Upregulated UCA1 and BMF in Gallbladder Epithelia of Children With Pancreaticobiliary Maljunction

Kaneko, Kenitiro*; Ito, Yoshinori; Ono, Yasuyuki*; Tainaka, Takahisa*; Tsuchiya, Hironori*; Shimoyama, Yoshie; Ando, Hisami*

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Background: Pancreaticobiliary maljunction is usually associated with choledochal cysts and often causes biliary carcinoma; however, the mechanism of carcinogenesis remains unknown. No study has analyzed overall changes in genetic expression beginning during childhood in gallbladder epithelia with pancreaticobiliary maljunction.

Patients and Methods: The genomewide expression of gallbladder epithelia was analyzed in 6 children with pancreaticobiliary maljunction and in 4 pediatric controls. Selected genes that were expressed differentially were further analyzed by the real-time reverse transcription-polymerase chain reaction (RT-PCR). The products of upregulated genes confirmed by real-time RT-PCR were immunohistochemically analyzed using gallbladders from 19 children with pancreaticobiliary maljunction, 5 pediatric controls, and 5 children with gallstones.

Results: Microarray analysis identified 188 upregulated and 160 downregulated genes. RT-PCR confirmed upregulation in 5 of 6 genes and downregulation in 1 of 5 genes, including UCA1, DUOX2, DUOXA2, ID1, BMF, and GP2. Immunohistochemistry showed a significantly higher expression of BMF in the pancreaticobiliary maljunction patients than in the controls and gallstone patients.

Conclusions: This study identified several deregulated genes in the gallbladder of children with pancreaticobiliary maljunction, which may contribute to the pathophysiology. UCA1, a noncoding RNA, is an oncofetal gene, and its upregulation may be important for biliary carcinogenesis. The elevated expression of BMF may function as an apoptotic activator in proliferative gallbladder epithelia.

Copyright 2011 by ESPGHAN and NASPGHAN


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