多发性骨髓瘤内质网应激相关特征的综合分析。

Integrative analysis of an endoplasmic reticulum stress-related signature in multiple myeloma.

机构信息

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of General Practice, Wuxi Branch of Ruijin Hospital, Jiangsu, China.

出版信息

J Gene Med. 2024 Jan;26(1):e3595. doi: 10.1002/jgm.3595. Epub 2023 Sep 20.

DOI:10.1002/jgm.3595

PMID:37730959

Abstract

BACKGROUND

Multiple myeloma (MM) is a malignancy in which plasma cells proliferate abnormally, and it remains incurable. The cells are characterized by high levels of endoplasmic reticulum stress (ERS) and depend on the ERS response for survival. Thus, we aim to find an ERS-related signature of MM and assess its diagnostic value.

METHODS

We downloaded three datasets of MM from the Gene Expression Omnibus database. After identifying ERS-related differentially expressed genes (ERDEGs), we analyzed them using Gene Ontology enrichment analysis. A protein-protein interaction network, a transcription factor-mRNA network, a miRNA-mRNA network and a drug-mRNA network were constructed to explore the ERDEGs. The clinical application of these genes was identified by calculating the infiltration of immune cells and using receiver operating characteistic analyses. Finally, qPCR was performed to further confirm the roles of ERDEGs.

RESULTS

We obtained nine ERDEGs of MM. Gene Ontology enrichment indicated that the ERDEGs played a role in the endoplasmic reticulum membrane. Additionally, the protein-protein interaction network showed interaction among the ERDEGs, and there were 20 proteins, 107 transcription factors, 42 drugs or molecular compounds and 51 miRNAs which were likely to interact with the nine genes. In addition, immune cell infiltration analyses showed that there was a strong correlation between the nine genes and immune cells, and these potential biomarkers exhibited good diagnostic values. Finally, the expression of ERDEGs in MM cells was different from that in healthy donor samples.

CONCLUSION

The nine ERS-related genes, CR2, DHCR7, DNAJC3, KDELR2, LPL, OSBPL3, PINK1, VCAM1 and XBP1 are potential biomarkers of MM, and this supports further clinical development of the diagnosis and treatment of MM.

摘要

背景

多发性骨髓瘤（MM）是一种浆细胞异常增殖的恶性肿瘤，目前仍无法治愈。这些细胞的特征是内质网应激（ERS）水平高，并且依赖 ERS 反应来存活。因此，我们旨在寻找 MM 的 ERS 相关特征，并评估其诊断价值。

方法

我们从基因表达综合数据库中下载了三个 MM 数据集。在鉴定出 ERS 相关差异表达基因（ERDEGs）后，我们使用基因本体论富集分析对其进行了分析。构建了蛋白质-蛋白质相互作用网络、转录因子-mRNA 网络、miRNA-mRNA 网络和药物-mRNA 网络，以探讨 ERDEGs。通过计算免疫细胞的浸润和使用接收器操作特征分析来确定这些基因的临床应用。最后，通过 qPCR 进一步验证 ERDEGs 的作用。

结果

我们获得了 MM 的九个 ERDEGs。基因本体论富集分析表明，ERDEGs 在内质网膜中发挥作用。此外，蛋白质-蛋白质相互作用网络显示 ERDEGs 之间存在相互作用，并且有 20 种蛋白质、107 种转录因子、42 种药物或分子化合物和 51 种 miRNA 可能与这九个基因相互作用。此外，免疫细胞浸润分析表明，这九个基因与免疫细胞之间存在很强的相关性，这些潜在的生物标志物具有良好的诊断价值。最后，MM 细胞中 ERDEGs 的表达与健康供体样本中的表达不同。