Bioinformatics Analysis to Screen the Key Genes and Pathways in the Formation of Early T-cell Precursor Acute Lymphoblastic Leukemia

Abstract

<sec><title>Purpose</title> Early T-cell precursor acute lymphoblastic leukemia (EPT-ALL) is a rare type of ALL that shows genetic characteristics of both ALL and acute myeloid leukemia (AML) but has a poorer prognosis and a higher recurrence rate. The aims of this study were to explore the underlying molecular mechanisms and specific biomarkers of EPT-ALL by bioinformatics analysis. </sec><sec><title>Methods</title> Two expression profile datasets (GSE8879 and GSE28703) were integrated to identify candidate genes of EPT-ALL. Differentially expressed genes (DEGs) between EPT-ALL and classic T-ALL were identified using edge R package. Protein–protein interaction (PPI) network clustering modules were analyzed with STRING and Cytoscape. In addition, the plugins of Cytoscape was used for hub gene functional enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and PPI network analysis. Survival analysis was performed by GEPIA and CCLE database. </sec><sec><title>Results</title> The GSE profiles shared 132 DEGs, including 63 upregulated genes and 69 downregulated genes. KEGG enrichment analysis of DEGs showed that the top 3 pathways were hematopoietic cell lineage, NF-kappaB signaling pathway and T cell receptor signaling pathway. Twenty-seven hub genes were identified from PPI by Cytoscape. High expression of ITGAM (integrin subunit alpha M) and LYN (LYN proto-oncogene) were associated with statistical significantly poorer overall survival rates by survival analysis using GEPIA database. Besides, LYN was differently expressed in EPT-ALL compared with classic T-ALL by searching in CCLE database. </sec><sec><title>Conclusion</title> We screened two hub genes which may consider as candidate novel biomarker in EPT. In summary, we elucidated LYN as a biomarker for the differentiation of EPT-ALL from classic T-ALL. </sec>