Gao Hai-Yan, Luo Xin-Guo, Chen Xi, Wang Jing-Hua
Department of Hematology, The Second Affiliated Hospital in Harbin Medical University, Harbin 150086, China.
Department of Hematology, Jinhua People's Hospital, Jinhua 321000, China.
Blood Cells Mol Dis. 2015 Jan;54(1):38-43. doi: 10.1016/j.bcmd.2014.08.002. Epub 2014 Sep 22.
The poor prognosis of pediatric acute lymphoblastic leukemia (ALL) indicates the existence of key candidate genes that affect pediatric ALL and its prognosis. The limma package in R was applied to screen differentially expressed genes (DEGs), and the Survival package and KMsurv package in R were used to screen disease free survival time related genes (prognosis genes). Then, based on latent pathway identification analysis (LPIA), latent pathways were identified, and pathway-pathway interaction network was constructed and visualized by Cytoscape. Based on the expression values of 8284 genes in 126 chips, 2796 DEGs and 353 prognosis genes were screened out. After overlapping DEGs and prognosis genes, 75 key genes were identified, which were most significantly enriched in 25 GO functions and chronic myeloid leukemia pathway. For the 75 key genes, 27 disease risk sub-pathways were identified, and HK3, HNMT, SULT2B1, KYNU, and PTGS2 were the significant key genes which were enriched in these sub-pathways. Furthermore, based on pathway-pathway interaction analysis, HK3 and PTGS2 were predicted as the most important genes. Through glycolysis and arachidonic acid metabolism, HK3 and PTGS2 might play important roles in pediatric ALL and its prognosis, and thus, might be potential targets for therapeutic intervention to suppress pediatric ALL.
小儿急性淋巴细胞白血病(ALL)的不良预后表明存在影响小儿ALL及其预后的关键候选基因。应用R语言中的limma软件包筛选差异表达基因(DEG),并使用R语言中的Survival软件包和KMsurv软件包筛选无病生存时间相关基因(预后基因)。然后,基于潜在通路识别分析(LPIA)识别潜在通路,并通过Cytoscape构建并可视化通路-通路相互作用网络。基于126个芯片中8284个基因的表达值,筛选出2796个DEG和353个预后基因。对DEG和预后基因进行重叠分析后,鉴定出75个关键基因,这些基因在25个GO功能和慢性粒细胞白血病通路中富集程度最高。对于这75个关键基因,鉴定出27个疾病风险子通路,HK3、HNMT、SULT2B1、KYNU和PTGS2是在这些子通路中富集的重要关键基因。此外,基于通路-通路相互作用分析,预测HK3和PTGS2是最重要的基因。通过糖酵解和花生四烯酸代谢,HK3和PTGS2可能在小儿ALL及其预后中发挥重要作用,因此,可能是抑制小儿ALL治疗干预的潜在靶点。