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基于单细胞 RNA-seq 和批量 RNA-seq 的骨髓增生异常综合征中坏死性凋亡相关诊断特征的综合分析。

Comprehensive analysis of a necroptosis-associated diagnostic signature for myelodysplastic syndromes based on single-cell RNA-seq and bulk RNA-seq.

机构信息

Department of Hematology, the First Hospital of Hebei Medical University, Shijiazhuang, China.

Department of Hematology, Shijiazhuang Ping'an Hospital, Shijiazhuang, China.

出版信息

Hereditas. 2024 Oct 15;161(1):38. doi: 10.1186/s41065-024-00335-x.

DOI:10.1186/s41065-024-00335-x

PMID:39407301

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11481600/

Abstract

BACKGROUND

Myelodysplastic syndromes (MDS) are heterogeneous and clonal hematological disorders. The role and mechanism of necroptosis in MDS remain poorly understood.

METHODS

mRNA expression profiles and single-cell RNA-sequencing (scRNA-seq) data were sourced from the GEO database. ScRNA-seq data were processed using the "Seurat" package. After cell annotation, necroptosis-related scores (NRscores) for each cell were calculated using the "UCell" package. Differentially expressed genes (DEGs) and their associated biological functions in NRscore-related cell populations were identified. Additionally, DEGs and necroptosis-related genes (DE-NRGs) between MDS patients and healthy controls were identified. Consensus clustering was employed to classify MDS patients into distinct subclusters based on DE-NRGs. The biological functions and immune characteristics of these classifications were analyzed. Prognostic gene signatures were determined using LASSO and SVM-RFE analyses, and a nomogram was constructed based on the prognostic gene signature.

RESULTS

A total of 12 cell types were identified in MDS and healthy controls. NRscore was found to be elevated in monocytes and common lymphoid precursors (CLPs). Enrichment analysis revealed that monocytes and CLPs with high NRscore were associated with mitochondria-related and immune-related pathways. Eleven DEGs in monocytes and CLPs between MDS patients and healthy controls were identified. Additionally, 13 DE-NRGs were identified from 951 DEGs between MDS and healthy controls. MDS patients were classified into two distinct subclusters based on these 13 DE-NRGs, revealing several immune-related processes and signaling pathways. Differences in immune subpopulations between the two subclusters were observed. A necroptosis-related diagnostic gene signature (IRF9, PLA2G4A, MLKL, BAX, JAK2, and STAT3) was identified as predictive of MDS prevalence.

CONCLUSION

Necroptosis plays a role in MDS progression by inducing inflammation. A novel necroptotic gene signature has been developed to distinguish and diagnose MDS at early stages of the disease.

摘要

背景

骨髓增生异常综合征（MDS）是一种异质性和克隆性的血液系统疾病。坏死性凋亡在 MDS 中的作用和机制仍知之甚少。

方法

从 GEO 数据库中获取 mRNA 表达谱和单细胞 RNA 测序（scRNA-seq）数据。使用“Seurat”软件包处理 scRNA-seq 数据。细胞注释后，使用“UCell”软件包计算每个细胞的坏死性凋亡相关评分（NRscore）。鉴定 NRscore 相关细胞群中差异表达基因（DEGs）及其相关生物学功能。此外，还鉴定了 MDS 患者与健康对照之间的 DEGs 和坏死性凋亡相关基因（DE-NRGs）。基于 DE-NRGs 将 MDS 患者分为不同的亚群进行共识聚类。分析这些分类的生物学功能和免疫特征。使用 LASSO 和 SVM-RFE 分析确定预后基因特征，并基于预后基因特征构建列线图。

结果

在 MDS 和健康对照中鉴定出 12 种细胞类型。发现单核细胞和共同淋巴祖细胞（CLP）中的 NRscore 升高。富集分析显示，NRscore 高的单核细胞和 CLP 与线粒体相关和免疫相关途径有关。在 MDS 患者和健康对照的单核细胞和 CLP 中鉴定出 11 个 DEGs。此外，还从 MDS 和健康对照之间的 951 个 DEG 中鉴定出 13 个 DE-NRGs。基于这 13 个 DE-NRGs，MDS 患者分为两个不同的亚群，揭示了几个免疫相关过程和信号通路。两个亚群之间观察到免疫亚群的差异。确定了一个与坏死性凋亡相关的诊断基因特征（IRF9、PLA2G4A、MLKL、BAX、JAK2 和 STAT3），可预测 MDS 的患病率。