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Abstract：
Acute 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.
摘要：
急性髓性白血病（AML）是一种生物异质性血液恶性肿瘤。进行这项研究以鉴定AML预后和治疗的潜在生物标志物。我们使用来自癌症基因组图谱(TCGA)的数据应用加权基因共表达网络分析来鉴定与AML预后相关的关键模块和枢纽基因。总的来说,在AML患者和健康对照之间鉴定出1581个差异表达基因(1096个上调和485个下调),蓝色模块是与AML形态学相关的14个模块中最重要的。通过功能富集分析,我们鉴定出蓝色模块中的217个基因显著富集于免疫应答途径中的中性粒细胞脱颗粒和中性粒细胞活化.存活分析显示六个基因(S100A9、S100A8、HK3、CD93、CXCR2和FGL2)位于显著富集的途径中,其与AML存活显著相关。我们在基因和单细胞水平上验证了这六个基因的表达，并确定了每个基因的甲基化位点，除了S100A8。最后,我们进行了体外实验,以证明鉴定出的hub基因是否与AML存活相关.在敲除CD93和FGL2后,在U937细胞系中细胞增殖在5天内显著降低。总之,我们确定CD93和FGL2是与AML生存相关的关键枢纽基因，FGL2是AML预后和治疗的新生物标志物。
