鉴定和研究多发性骨髓瘤预后模型中的铜死亡相关基因。
Identification and study of cuproptosis-related genes in prognostic model of multiple myeloma.
机构信息
Shanxi Medical University, Taiyuan, People's Republic of China.
Department of Hematology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, People's Republic of China.
出版信息
Hematology. 2023 Dec;28(1):2249217. doi: 10.1080/16078454.2023.2249217.
BACKGROUND
Multiple myeloma (MM) is a highly heterogeneous disease. Cuproptosis is a novel mode of death that is closely associated with several diseases, such as hepatocellular carcinoma. However, its role in MM is unknown.
METHODS
MM transcriptomic and clinical data were obtained from UCSC Xena and gene expression omnibus (GEO) databases. Following MM samples were divided into different subtypes based on the cuproptosis genes, the differentially expressed genes (DEGs) among different subtypes, namely, candidate cuproptosis related genes were analyzed by univariate Cox and least absolute shrinkage and selection operator (LASSO) regression to construct a cuproptosis-related risk model. After the independent prognostic analysis was performed, a nomogram was constructed. Finally, Functional enrichment analysis and immune infiltration analysis were performed in the high- and low-risk groups, potential therapeutic agents were then predicted.
RESULTS
The 784 MM samples in UCSC Xena cohorts were divided into three different subtypes, and 4 out of 346 candidate cuproptosis related genes, namely CDKN2A, BCL3, KCNA3 and TTC14 were used to construct a risk model. Risk score was considered a reliable independent prognostic factor for MM patients. It was investigated that the pathway of cell cycle was significantly enriched in the high-risk group. In addition, immune score, ESTIMATE score and cytolytic activity were significantly different between different risk groups, as well as 13 immune cells such as memory B cells. Nine drugs were predicted in our study.
CONCLUSION
A cuproptosis-related prognostic model was constructed, which may have a potential guiding role in the treatment of MM.
背景
多发性骨髓瘤（MM）是一种高度异质性疾病。铜死亡是一种新的死亡方式，与肝癌等多种疾病密切相关。然而，其在 MM 中的作用尚不清楚。
方法
从 UCSC Xena 和基因表达综合（GEO）数据库中获取 MM 转录组学和临床数据。根据铜死亡基因将 MM 样本分为不同亚型，通过单变量 Cox 和最小绝对值收缩和选择算子（LASSO）回归分析不同亚型之间的差异表达基因（DEGs），以构建铜死亡相关风险模型。进行独立预后分析后，构建列线图。最后，在高风险组和低风险组中进行功能富集分析和免疫浸润分析，预测潜在的治疗药物。
结果
UCSC Xena 队列中的 784 例 MM 样本被分为三个不同亚型，在 346 个候选铜死亡相关基因中，有 4 个基因（CDKN2A、BCL3、KCNA3 和 TTC14）被用于构建风险模型。风险评分被认为是 MM 患者可靠的独立预后因素。研究发现，高风险组细胞周期途径显著富集。此外，不同风险组之间的免疫评分、ESTIMATE 评分和细胞溶解活性以及记忆 B 细胞等 13 种免疫细胞均有显著差异。在本研究中预测了 9 种药物。
结论
构建了一个铜死亡相关预后模型，该模型可能对 MM 的治疗具有潜在的指导作用。
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