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: 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.