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*

Journal of Pediatric Gastroenterology & Nutrition: June 2011 - Volume 52 - Issue 6 - p 744–750
doi: 10.1097/MPG.0b013e318214bd30
Original Articles: Hepatology and Nutrition

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.

*Department of Pediatric Surgery, Japan

Department of Pediatrics, Japan

Department of Pathology and Laboratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Received 8 December, 2010

Accepted 6 February, 2011

Address correspondence and reprint requests to Kenitiro Kaneko, MD, Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan (e-mail: kkaneko@med.nagoya-u.ac.jp).

Funding was provided by a Grant-in-aid (21592275) for Scientific Research from the Japan Society for the Promotion of Science.

The authors report no conflicts of interest.

Copyright 2011 by ESPGHAN and NASPGHAN