The novel prognostic analysis of AML based on ferroptosis and cuproptosis related genes

IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
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Abstract

Background

Acute myeloid leukemia (AML) is a hematological malignancy. The aim of this research was to develop a ferroptosis and cuproptosis related novel prognostic signature associated with AML.

Methods

The ferroptosis and cuproptosis related genes correlated with the prognosis of AML were identified by univariate Cox analysis. The consistent cluster analysis was performed for 150 AML patients in TCGA dataset. The key module genes associated with GSVA score of ferroptosis and cuproptosis were identified by WGCNA. univariate Cox and LASSO regression analysis were adopted to build a ferroptosis and cuproptosis AML prognostic signature. Finally, the expression of five prognostic genes in clinical tissue samples were verified by RT-qPCR.

Results

A grand total of 27 FCRGs associated with AML prognosis were identified.Then, two AML sub-types with significantly different survival were obtained. We found 3 significantly differential expressed immune cells (naive CD4 cells, regulatory T cells and resting mast cells) between two risk sub-groups. Meanwhile, ‘IL6 JAK STAT3 signaling’ and ‘P53 pathway’ were enriched in low-risk group. A ferroptosis and cuproptosis related prognostic signature was build based on 8 prognostic genes. RT-qPCR results indicated that there was no significant difference in the expression of OLFML2A and CD109 between AML and normal samples. However, compared to the control group, LGALS1, SOCS1, and RHOC showed significantly lower expression in the AML group.

Conclusion

The prognostic signature comprised of OLFML2A, LGALS1, ABCB11, SOCS1, RHOC, CD109, RD3L and PTPN13 based on ferroptosis and cuproptosis was established, which provided theoretical basis for the research of AML.

基于铁突变和杯突变相关基因的新型急性髓细胞性白血病预后分析
背景急性髓性白血病(AML)是一种血液恶性肿瘤。方法 通过单变量 Cox 分析确定了与急性髓性白血病预后相关的铁和铜相关基因。对 TCGA 数据集中的 150 例 AML 患者进行了一致的聚类分析。采用单变量 Cox 和 LASSO 回归分析,建立了铁突变和杯突变急性髓细胞性白血病预后特征。最后,通过 RT-qPCR 验证了 5 个预后基因在临床组织样本中的表达。结果共鉴定出 27 个与急性髓细胞性白血病预后相关的 FCRGs。我们发现,在两个风险亚型中,3种免疫细胞(幼稚CD4细胞、调节性T细胞和静止肥大细胞)的表达存在明显差异。同时,"IL6 JAK STAT3 信号 "和 "P53 通路 "在低风险组中富集。基于 8 个预后基因,建立了与铁突变和杯突变相关的预后特征。RT-qPCR 结果表明,急性髓细胞和正常样本中 OLFML2A 和 CD109 的表达无明显差异。结论 建立了由 OLFML2A、LGALS1、ABCB11、SOCS1、RHOC、CD109、RD3L 和 PTPN13 组成的基于铁突变和杯突变的预后特征,为 AML 的研究提供了理论依据。
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来源期刊
CiteScore
6.60
自引率
2.90%
发文量
202
审稿时长
85 days
期刊介绍: The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods. Also, we only publish those articles in which the quality assurance regarding the execution of experiments and achievement of results is guaranteed.
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