Identification of Potential Biomarkers and Pathways in Acute Myeloid Leukemia: Correlation Between the Calcineurin Signaling Pathway and Vascular Brittleness in Acute Myeloid Leukemia.

Homood Alharbi, Mohammad Ahmad, Zhong Cui, Dong Meng, Ying Xin, Xues Yan
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Abstract

Objective: In this study, clinical bioinformatics analysis was used to identify potential biomarkers of acute myeloid leukemia (AML) occurrence and development, drug resistance, and poor prognosis to provide a theoretical basis for the treatment of AML.

Methods: On the basis of the TCGA, GEO, and GTEx databases, an AML secondary database was established, and differential expression analysis and WGCNA were carried out to identify genes related to the prognosis of AML patients. Survival analysis was carried out for internal verification of key genes, and GEO data were used for external verification to obtain core genes related to prognosis. For differentially expressed genes, the EpiMed platform independently developed by the team was used for drug prediction.

Results: A total of 36 overlapping genes were obtained via difference analysis and WGCNA. Enrichment analysis revealed that the overlapping genes were associated with neutrophil activation, transcription dysregulation, AML, apoptosis, and other biological indicators. A protein interaction network was constructed for NCOA4, ACSL4, DPP4, ATL1, MT1G, ALOX15, and SLC7A11, which are key genes. Survival analysis revealed that NCOA4, ACSL4, DPP4, and ATL1 significantly affected the survival of patients with AML. The GSE142698 dataset verified that MPO, BCL2A1, and STMN1 had a statistically significant impact on the survival of AML patients.

Conclusion: NCOA4, ACSL4, DPP4, and ATL1 may be potential biomarkers related to the survival and prognosis of patients with AML, and the calcineurin signaling pathway is associated with the risk of vascular fragility in AML patients, which can provide a reference for further research and optimization of treatment regimens.

急性髓性白血病潜在生物标志物和通路的鉴定:钙调磷酸酶信号通路与急性髓性白血病血管脆性的相关性
目的:本研究通过临床生物信息学分析,鉴定急性髓系白血病(acute myeloid leukemia, AML)发生发展、耐药、预后不良的潜在生物标志物,为AML的治疗提供理论依据。方法:在TCGA、GEO、GTEx数据库的基础上,建立AML二级数据库,进行差异表达分析和WGCNA,鉴定与AML患者预后相关的基因。采用生存分析对关键基因进行内部验证,采用GEO数据进行外部验证,获得与预后相关的核心基因。对于差异表达基因,使用团队自主开发的EpiMed平台进行药物预测。结果:通过差异分析和WGCNA共获得36个重叠基因。富集分析显示重叠基因与中性粒细胞活化、转录失调、AML、细胞凋亡等生物学指标相关。构建了关键基因NCOA4、ACSL4、DPP4、ATL1、MT1G、ALOX15、SLC7A11的蛋白相互作用网络。生存分析显示,NCOA4、ACSL4、DPP4和ATL1显著影响AML患者的生存。GSE142698数据集证实MPO、BCL2A1和STMN1对AML患者的生存有统计学显著影响。结论:NCOA4、ACSL4、DPP4和ATL1可能是与AML患者生存和预后相关的潜在生物标志物,钙调磷酸酶信号通路与AML患者血管易损风险相关,可为进一步研究和优化治疗方案提供参考。
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