利用公共数据深入挖掘食管鳞状细胞癌候选肿瘤抑制基因

Deciphering the Potential Tumor Suppressor Genes in Esophageal Squamous Cell Carcinoma Based on Public Database

[目的]自20世纪90年代开始,人们利用杂合性缺失(loss of heterozygosity,LOH)技术寻找引起食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)癌变的肿瘤抑制基因。但除了TP53、CDKN2A等以外,目前很多高频LOH区域的抑癌基因仍未发现。随着近年来生物学信息公共数据库的建设发展,有必要重新筛选分析ESCC中的潜在抑癌基因。[方法]利用Pubmed检索1991～2012年间的食管癌LOH文章,整理信息,综合考虑LOH频率和文献重复鉴定次数后,利用Circos软件绘制并确认了ESCC中高度可信LOH热点区域。对每一区域,利用人类基因组数据库、肿瘤抑制基因数据库和人类蛋白质图集数据库分析其中的候选抑癌基因。[结果]基于85篇针对ESCC的LOH相关文献,共确定10个ESCC高度可信LOH热点区域,主要累及3p、5q、9p、13q、17p、17q等染色体臂。基于3个公共数据库的分析,在每个区域中均确定了一个以上的候选抑癌基因,其中很多基因从未在ESCC中受到关注。[结论]综合考虑文献中对LOH区域的可重复鉴定性可避免原始文献质量和样本选择偏倚等的干扰。利用公共数据库深入挖掘ESCC中的候选抑癌基因,为后续选择合适的靶基因开展深入的表达和功能分析提供了理论依据。

[Purposel Since the early years of 1990s,people used the loss of heterozygosity （LOH） technology to find the tumor suppressor genes which led to tumorigenesis of esophageal squamous cell carcinoma（ESCC）. However, the tumor suppressor genes in several high-frequency LOH regions remained to be discovered,except for TP53 and CDKN2A etc. With the development of public databases in recent years,it is necessary to re-analyze the potential tumor suppressor genes in ESCC. [Methods] Pubmed retrieved using the key phrase ＇esophageal squamous cell carcinoma AND Loss of Heterozygosity＇. Literature published between 1991 and 2012 were obtained. After considering the LOH frequency and repeatability in literature,the high-confidence LOH hot regions in ESCC were showed and confirmed using the Cireos software. For each region,the candidate tumor suppressor genes were analyzed using three public databases,including the human genome database,the tumor suppressor gene database and the human protein atlas database. [Resultsl Based on 85 papers,a to- tal of 10 high-confidence LOH hot regions in ESCC were identified,which mainly involved in 3p, 5q,9p, 13q, 17p, 17q chromosomes. After the analysis based on three public databases,one or more candidates tumor suppressor genes were determined, many of which had never been concerned in ES- CC. [Conclusion] Considering the repeatable identification of LOH regions in the literature can avoid the interference of the poor papers quality and bias on sample selection. Deciphering the can- didate tumor suppressor genes in ESCC using public databases can provide a theoretical basis for the in-depth genes expression and functional analysis.