Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai 201102, China.
World J Gastroenterol. 2011 Feb 14;17(6):796-803. doi: 10.3748/wjg.v17.i6.796.
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.
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.
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.
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.
分析胆道闭锁（BA）患者肝脏中差异表达的基因谱，确定在 BA 发病机制中起核心作用的基因、功能类别和途径，以及鉴定 BA 的新预后标志物。
收集对照组、新生儿胆汁淤积组和 BA 患者（<60 d、60-90 d 和>90 d）的肝组织样本进行 DNA 微阵列分析。使用基因本体论系列检验聚类和通路发现者软件进行生物信息学分析。通过逆转录聚合酶链反应（RT-PCR）对选定基因的变化进行验证。在一项为期 2 年的随访研究中，分析 RRAS 基因表达与 40 例 BA 患者预后的关系。
这 4 个确定的显著基因表达谱可以将 BA 肝组织与正常和其他疾病肝组织明显区分开。包含的基因主要参与炎症反应和细胞外基质的重建。与 BA 相关的显著途径主要涉及自身免疫反应、T 淋巴细胞的激活及其相关细胞因子。RRAS、POMC、SLC26A6 和 STX3 基因是 BA 发病机制中的重要调节模块。RRAS 的表达与黄疸消退率呈负相关，与胆管炎发生率呈正相关。
T 淋巴细胞介导的自身免疫反应可能在 BA 的发病机制中起重要作用。RRAS 基因是 BA 发病机制中的重要调节模块，可能作为 BA 的新预后标志物。
