Identification of key candidate genes and miRNA‑mRNA target pairs in chronic lymphocytic leukemia by integrated bioinformatics analysis

Mol Med Rep. 2019 Jan;19(1):362-374. doi: 10.3892/mmr.2018.9636. Epub 2018 Nov 9.

Abstract

Chronic lymphocytic leukemia (CLL) is a malignant clonal proliferative disorder of B cells. Inhibition of cell apoptosis and cell cycle arrest are the main pathological causes of this disease, but its molecular mechanism requires further investigation. The purpose of the present study was to identify biomarkers for the early diagnosis and treatment of CLL, and to explore the molecular mechanisms of CLL progression. A total of 488 differentially expressed genes (DEGs) and 32 differentially expressed microRNAs (miRNAs; DEMs) for CLL were identified by analyzing the gene chips GSE22529, GSE39411 and GSE62137. Functional and pathway enrichment analyses of DEGs demonstrated that DEGs were mainly involved in transcriptional dysregulation and multiple signaling pathways, such as the nuclear factor‑κB and mitogen‑activated protein kinase signaling pathways. In addition, Cytoscape software was used to visualize the protein‑protein interactions of these DEGs in order to identify hub genes, which could be used as biomarkers for the early diagnosis and treatment of CLL. Cytoscape software was also used to analyze the association between the predicted target mRNAs of DEMs and DEGs and increase knowledge about the miRNA‑mRNA regulatory network associated with the progression of CLL. Taken together, the present study provided a bioinformatics basis for advancing our understanding of the pathogenesis of CLL by identifying differentially expressed hub genes, miRNA‑mRNA target pairs and molecular pathways. In addition, hub genes may be used as novel biomarkers for the diagnosis of CLL and to guide the selection of CLL drug combinations.

Keywords: chronic lymphocytic leukemia; bioinformatics analysis; protein-protein interaction network; hub genes; microRNA-mRNA network.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Computational Biology / methods*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Ontology
  • Gene Regulatory Networks*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • MicroRNAs / genetics*
  • Protein Interaction Maps
  • RNA, Messenger / genetics*
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Messenger