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.
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.
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.
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: email@example.com).
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.