Identification of key genes affecting disease free survival time of pediatric acute lymphoblastic leukemia based on bioinformatic analysis

Blood Cells Mol Dis. 2015 Jan;54(1):38-43. doi: 10.1016/j.bcmd.2014.08.002. Epub 2014 Sep 22.

Abstract

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.

Keywords: Differentially expressed genes; Disease free survival time; Function enrichment; Pathway–pathway interactions; Pediatric acute lymphoblastic leukemia.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Computational Biology
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Leukemic*
  • Genes, Neoplasm*
  • Humans
  • Infant
  • Male
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Survival Rate

Substances

  • Neoplasm Proteins