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Identification and immunoassay of prognostic genes associated with the complement system in acute myeloid leukemia

髓系白血病 肿瘤科 医学 基因 弗雷明翰风险评分 基因表达谱 内科学 白血病 比例危险模型 多元分析 免疫学 计算生物学 基因表达 生物 疾病 遗传学
作者
Chen Liu,Lin Liu
出处
期刊:Journal of the Formosan Medical Association [Elsevier BV]
卷期号:123 (8): 904-915 被引量:2
标识
DOI:10.1016/j.jfma.2024.01.024
摘要

Studies have associated the development of pulmonary leukemia with the activation of the complement system. However, the roles and mechanisms of complement system-related genes (CSRGs) in acute myeloid leukemia (AML) have not been investigated extensively. This study used The Cancer Genome Atlas (TCGA)-AML and GSE37642 datasets. Differentially expressed CSRGs (CSRDEGs) were identified by overlapping genes differentially expressed between the high and low CSRG score groups and key module genes identified in a weighted gene co-expression network analysis. Univariate and multivariate Cox analyses identified CSRG-related biomarkers, which were used to build a prognostic model. After gene set enrichment analysis (GSEA), immune-related and drug-sensitivity analyses were performed in the high- and low-risk groups. Four prognosis-related biomarkers were identified and used to develop a prognostic model: MEOX2, IGFBP5, CH25H, and RAB3B. The model's performance was verified in a test cohort (a subset of samples from the TCGA-AML dataset) and a validation cohort (GSE37642). The GSEA revealed that the high-risk group was mainly enriched for Golgi organization and cytokine-cytokine receptor interactions, and the low-risk group was mainly enriched in the hedgehog signaling pathway and spliceosome. Lastly, two immune cells were found to show differential infiltration between risk groups, which correlated with the risk scores. M1 macrophage infiltration was significantly positively correlated with RAB3B expression. Sensitivity to 36 drugs differed significantly between risk groups. This study screened four CSRG-related biomarkers (MEOX2, IGFBP5, CH25H, and RAB3B) to provide a basis for predicting AML prognosis.

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