Objectives: To explore the underlying molecular mechanisms of childhood B-precursor acute lymphoblastic leukemia (ALL) by bioinformatics analysis and find potential targets for childhood ALL diagnosis and treatment.
Methods: Gene expression profile GSE28460 was downloaded from the Gene Expression Omnibus, including 49 diagnostic and relapse bone marrow samples with childhood B-precursor ALL. The differentially expressed genes (DEGs) were identified by paired t-test. Pathway enrichment analysis of DEGs and transcription factors (TFs) enrichment analysis were performed, followed by construction of co-expressed, DEGs, and susceptibility gene protein-protein interaction (PPI) network. Based on these three networks, relevant regulatory network modules and the important DEGs in the modules were identified.
Results: Total of 947 DEGs were identified. Up-regulated DEGs enriched 20 pathways including cell cycle, and down-regulated DEGs significantly enriched Jak-STAT signaling pathways. CDK1 and BRCA1 were found to have more hubs in both co-expressed network and PPI network. Besides, total of five modules in INTS10, MCM, BRCA1, GYPA, and VCAN1 families were identified and a pathway of INTS10-INTS6-POLR2A-MAGI2 was selected.
Conclusion: Cell cycle and Jak-STAT signaling pathway were closely associated with relapse of childhood B-precursor ALL. The DEGs, such as PTTG1, PIK3CA, CDK1, and BRCA1 may be the potential targets for childhood ALL diagnosis and treatment.
Keywords: Acute lymphoblastic leukemia; Bioinformatics analysis; Molecular mechanism; Network module.