Integrative analysis of an endoplasmic reticulum stress-related signature in multiple myeloma
Integrative analysis of an endoplasmic reticulum stress-related signature in multiple myeloma
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DOI：
10.1002/jgm.3595
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发表时间：
2023-09-20
影响因子：
3.5
通讯作者：
Yan，Hua
中科院分区：
文献类型：
--
作者：
Wu，Chengyu;Liu，Mei;Yan，Hua
背景多发性骨髓瘤（multiple myeloma，MM）是浆细胞异常增殖的恶性肿瘤，目前仍无法治愈.这些细胞的特征是高水平的内质网应激（ERS），并依赖于ERS反应生存。因此，我们的目标是找到一个ERS相关的签名MM和评估其诊断value.MethodsWe下载三个数据集MM基因表达综合数据库。在确定ERS相关的差异表达基因（ERDEG）后，我们使用基因本体富集分析对其进行了分析。通过构建蛋白质-蛋白质相互作用网络、转录因子-mRNA网络、miRNA-mRNA网络和药物-mRNA网络来研究ERDEG。通过计算免疫细胞浸润和受试者操作特征分析，确定这些基因的临床应用。最后，qPCR进一步证实ERDEGs的作用。结果我们获得了9个ERDEGs的MM。基因本体富集表明，ERDEGs发挥作用的内质网膜。蛋白质-蛋白质相互作用网络显示ERDEG之间存在相互作用，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miRNAs可能与这9个基因相互作用。此外，免疫细胞浸润分析表明，9个基因和免疫细胞之间存在很强的相关性，这些潜在的生物标志物显示出良好的诊断价值。结论CR2、DHCR 7、DNAJC 3、KDELR 2、LPL、OSBPL 3、PINK 1、VCAM 1和XBP 1等9个ERS相关基因是MM的潜在生物标志物，为MM的临床诊断和治疗提供了新的思路。
BackgroundMultiple 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.MethodsWe 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.ResultsWe 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.ConclusionThe 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.