胃癌患病风险关键基因筛选

Bioinformatics analysis of the key risk genes in gastric cancer

目的:筛选胃癌患病风险关键基因,为进一步相关性研究提供参考。方法:检索Pubmed/Medline和Embase数据库,收集胃癌患病风险相关基因的文献,运用生物信息学的方法对获得的基因进行分析。结果:954篇文献符合要求,共涉及268个基因,其中不同功能的GO分类780种,京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路67种,而贝叶斯因子>1、P≤0.001且误判率≤0.001的GO分类有94种,KEGG通路有6种,主要涉及应激反应、DNA损伤修复、细胞生理调控过程、细胞凋亡、免疫反应、细胞因子与细胞因子受体相互作用、Toll样受体信号通路、Jak-STAT信号通路以及MAPK信号通路相关。所涉及基因的蛋白产物通过在线String 9.0软件构建蛋白网络,运用Cytoscape 2.8.2软件将构建的蛋白网络图可视化及量化。筛出24个关键候选基因,包括STAT3、EGFR、NFKB1、GSTP1、IL4、IFNG、PARP1、MMP9、JUN、IL6、TNF、IL1B、CD4、CDH1、SMAD4、HRAS、PTGS2、EGF、VEGFA、MLH1、TP53、CASP3、TGFB1和CCND1,其中5个关键基因是PTGS2、TNF、IL6、NFKB1和TP53。结论:胃癌患病风险关键基因可为胃癌遗传易感性研究提供参考,针对这些基因的大样本跨种族及高质量的临床研究可能是未来的方向。

OBJECTIVE：To screen the key risk genes associated with gastric cancer for further study. METHODS： Pubmed/MedIine,Embase databases were searched to collect literatures on risk genes associated with gastric cancer. The genes were analyzed with bioinformaties method. RESULTS： Totally 954 articles meeted the requirements and 268 stomach cancer risk genes were got, which mainly related to stress reaction, DNA damage repair, cellular physiological process, ap- optosis,immune response,and cytokine-cytokine receptor interaction,Toll-like receptor signaling pat hway,Jak-STAT sig- naling pathway,as well as MAPK signal pathway. A total of 780 functional classifications by the Gene ontology （G（）） and 67 pathways by the Kyoto Encyclopedia of Genes and Genomes （KEGG） were involved. Among these risk genes,only 94 G（） classifications and 6 KEGG pathways were significant （Bayes factor≥ 1 and P value≤0. 001）. Cytoscape software 2.8.2 was used to make the proteins （translated by the genes） network map visualized,and which quantitated by online String software. Twenty-four key candidate genes （STAT3, EGFR, NFKB1, GSTP1, IL4, IFNG, PARP1, MMP9, JUN, IL6, TNF, IL1B, CD4, CDH1, SMAD4, HRAS, PTGS2, EGF, VEGFA, MLH1, TP53, CASP3, TGFB1, CCND1 ） were screened out and 5 of them （PTGS2 ,TNF,IL6 ,NFKB1 ,TP53） were key genes. CONCLUSION：Those key risk genes may offer a new thought to the studies of genetic susceptibility to gastric cancer, and high quality clinical studies with large samples on those genes may be the direction of future.