Brief Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 14, 2011; 17(6): 796-803
Published online Feb 14, 2011. doi: 10.3748/wjg.v17.i6.796
RRAS: A key regulator and an important prognostic biomarker in biliary atresia
Rui Zhao, Hao Li, Chun Shen, Shan Zheng
Rui Zhao, Hao Li, Chun Shen, Shan Zheng, Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai 201102, China
Author contributions: Zhao R wrote the manuscript and performed the majority of experiments; Li H and Shen C coordinated and provided the collection of all the human materials; Zheng S designed the study and provided the financial support for this work.
Supported by National Natural Science Foundation of China, No. 30973139
Correspondence to: Shan Zheng, MD, Department of Pediatric Surgery, Children’s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102, China. szheng@shmu.edu.cn
Telephone: +86-21-64931007 Fax: +86-21-64931901
Received: September 14, 2010
Revised: November 3, 2010
Accepted: November 10, 2010
Published online: February 14, 2011
Abstract

AIM: To characterize the differentially expressed gene profiles in livers from biliary atresia (BA) patients including, ascertain genes, functional categories and pathways that play a central role in the pathogenesis of BA, and identify the novel prognostic markers for BA.

METHODS: Liver tissue samples from control patients, neonatal cholestasis patients, and BA patients at the age of < 60 d, 60-90 d, and > 90 d were pooled for DNA microarray analysis. Bioinformatics analysis was performed using, series test cluster of gene ontology, and Pathway-Finder software. Reverse-transcription polymerase chain reaction was performed to confirm changes in selected genes. Relation between RRAS gene expression and prognosis of 40 BA patients was analyzed in a 2-year follow-up study.

RESULTS: The 4 identified significant gene expression profiles could confidently separate BA liver tissue from normal and other diseased liver tissues. The included genes were mainly involved in inflammation response and reconstruction of cellular matrix. The significant pathways associated with BA were primarily involved in autoimmune response, activation of T lymphocytes and its related cytokines. The RRAS, POMC, SLC26A6 and STX3 genes were important regulatory modules in pathogenesis of BA. The expression of RRAS was negatively correlated with the elimination rate of jaundice and positively correlated with the occurrence rate of cholangitis.

CONCLUSION: Autoimmune response mediated by T lymphocytes may play a vital role in the pathogenesis of BA. The RRAS gene is an important regulatory module in the pathogenesis of BA, which may serve as a novel prognostic marker for BA.

Keywords: Biliary atresia, DNA microarray, Bioinformatics, RRAS, Prognostic biomarker