Affiliation:
1. Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of Medicine, Hangzhou City University Hangzhou China
2. College of Life Sciences, Zhejiang Normal University Jinhua China
Abstract
AbstractAcute myeloid leukaemia (AML) is a biologically heterogeneous haematological malignancy. This study was performed to identify the potential biomarkers for the prognosis and treatment of AML. We applied weighted gene co‐expression network analysis to identify key modules and hub genes related to the prognosis of AML using data from The Cancer Genome Atlas (TCGA). In total, 1581 differentially expressed genes (1096 upregulated and 485 downregulated) were identified between AML patients and healthy controls, with the blue module being the most significant among 14 modules associated with AML morphology. Through functional enrichment analysis, we identified 217 genes in the blue module significantly enriched in ‘neutrophil degranulation’ and ‘neutrophil activation involved in immune response’ pathways. The survival analysis revealed six genes (S100A9, S100A8, HK3, CD93, CXCR2 and FGL2) located in the significantly enriched pathway that were notably related to AML survival. We validated the expression of these six genes at gene and single‐cell levels and identified methylation loci of each gene, except for S100A8. Finally, in vitro experiments were performed to demonstrate whether the identified hub genes were associated with AML survival. After knockdown of CD93 and FGL2, cell proliferation was significantly reduced in U937 cell line over 5 days. In summary, we identified CD93 and FGL2 as key hub genes related to AML survival, with FGL2 being a novel biomarker for the prognosis and treatment of AML.
Funder
Natural Science Foundation of Zhejiang Province
National Natural Science Foundation of China