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急性髓系白血病中坏死性凋亡相关基因的筛选及其预后能力、临床价值以及其拷贝数变异影响的评估

英文原题：Screening of necroptosis-related genes and evaluating the prognostic capacity, clinical value, and the effect of their copy number variations in acute myeloid leukemia.

查看英文原题

Screening of necroptosis-related genes and evaluating the prognostic capacity, clinical value, and the effect of their copy number variations in acute myeloid leukemia.

PubMed 2025/01/13（内容时间） BMC Cancer Q2 · IF 4.1（JCR 2025）

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技术：NK 细胞急性髓系白血病地区：中国
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研究概要

这些筛选出的 NRDEGs 可作为 AML 患者的临床预后预测指标，以及诊断和治疗靶向的潜在生物标志物。

研究思路结论见上方概要

背景

急性髓系白血病（AML）是一种侵袭性血液系统肿瘤。过去几十年间，其生存率改善甚微。坏死性凋亡与某些类型恶性肿瘤的结局相关。在此，我们评估了坏死性凋亡相关基因（NRGs）在AML中的诊断能力、预后价值及其拷贝数变异（CNVs）的影响。

方法

将GEO数据库中的差异表达基因（DEGs）与GeneCards、MSigDB和文献中的NRGs取交集后，鉴定出坏死性凋亡相关差异表达基因（NRDEGs）。应用机器学习获得hub-NRDEGs。在体外验证hub-NRDEGs的表达水平。使用Cytoscape筛选hub-NRDEGs的mRNA-miRNA和mRNA-TF相互作用网络。利用ssGSEA计算hub-NRDEGs与免疫细胞之间的相关性。在TCGA数据库的TCGA-LAML数据集上对hub-NRDEGs进行CNV分析。利用Kaplan-Meier（K-M）生存分析结合Cox模型评估预后价值。

结果

获得了6个hub-NRDEGs（SLC25A5、PARP1、CTSS、ZNF217、NFKB1和PYGL），并可视化了其在AML中由CNVs导致的表达变化。共筛选出65个mRNA-miRNA和80个mRNA-TF与hub-NRDEGs的相互作用网络。ssGSEA结果显示，在AML中RAPR1的表达与CD56 dimNK 细胞呈负相关，CTSS的表达与髓源性抑制细胞（MDSCs）呈正相关。K-M结果表明，ZNF217在AML患者生存时间方面存在显著差异。Cox回归模型显示，hub-NRDEGs在第1年和第5年具有更好的预测能力。

展开英文摘要原文
BACKGROUND

Acute myeloid leukemia (AML) is an aggressive hematological neoplasm. Little improvement in survival rates has been achieved over the past few decades. Necroptosis has relationship with certain types of malignancies outcomes. Here, we evaluated the diagnostic ability, prognostic capacity of necroptosis-related genes (NRGs) and the effect of their copy number variations (CNVs) in AML.

METHODS

Necroptosis-related differentially expressed genes (NRDEGs) were identified after intersecting differentially expressed genes (DEGs) from the Gene Expression Omnibus(GEO) database with NRGs from GeneCards, the Molecular Signatures Database (MSigDB) and literatures. Machine learning was applied to obtain hub-NRDEGs. The expression levels of the hub-NRDEGs were validated in vitro. The mRNA-miRNA and mRNA-TF interaction networks with the hub-NRDEGs were screened using Cytoscape @ . Single-sample gene set enrichment analysis (ssGSEA) was utilized to calculate correlations between the hub-NRDEGs and immune cells. CNV analysis of the hub-NRDEGs was carried out on the TCGA-LAML datasets from the TCGA database. Kaplan-Meier (K-M) survival analyses were utilized to evaluate the prognostic values along with Cox model.

RESULTS

Six hub-NRDEGs (SLC25A5, PARP1, CTSS, ZNF217, NFKB1, and PYGL) were obtained and their expression changes derived from CNVs in AML were visualized. In total, 65 mRNA-miRNA and 80 mRNA-TF interaction networks with hub-NRDEGs were screened. The ssGSEA result showed the expression of RAPR1 was inversely related to CD56 dim natural killer cells and the expression of CTSS was positive related to Myeloid-derived suppressor cells (MDSCs) in AML. The K-M results demonstrated that ZNF217 had significant difference in the duration of survival in AML patients. Cox regression models revealed that the hub-NRDEGs had better predictive power at year-1 and year-5.

CONCLUSION

These screened NRDEGs can be exploited as clinical prognostic predictions in AML patients, as well as potential biomarkers for diagnosis and therapeutic targeting.

论文信息

作者
Wen D、Yan R、Zhang L、Zhang H、Chen X、Zhou J
第一作者单位
The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi Children's Hospital, Wuxi, 214023, China.China
通讯作者单位
The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi Children's Hospital, Wuxi, 214023, China. jianzhou@njmu.edu.cn.China
期刊
BMC cancer2025 Jan 13
原文标识
PubMed 39806277　·　DOI 10.1186/s12885-025-13439-y

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