Chen Xi-Tian, Wu Yi-Peng, Li Yong-Qing, Chen Qi, Yao Le-Yang, Lin Lin, Gao Gui-Yang
Department of Hematology, Jieyang People's Hospital, Jieyang, China.
Department of Brain Centre, Jiexi County second People's Hospital, Jieyang, China.
Medicine (Baltimore). 2025 Mar 7;104(10):e41707. doi: 10.1097/MD.0000000000041707.
Multiple myeloma (MM) is an incurable hematologic malignancy, with chemotherapy being the primary treatment. However, the development of drug resistance remains a major challenge. This study aimed to identify therapeutic targets associated with drug resistance in MM and assess their prognostic significance. Gene expression data from GSE82307, GSE146649, and GSE136725 were analyzed to identify differentially expressed genes (DEGs) using the "limma" and "RobustRankAggreg" R packages. Functional enrichment analysis and protein-protein interaction (PPI) network analysis were performed, with key network modules identified using Cytoscape. The expression and prognostic relevance of DEGs were validated using MM patient samples from the GSE136725 and MMRF CoMMpass databases. A total of 4623 DEGs were identified, and robust rank aggregation analysis revealed the top 20 upregulated genes. Among them, AURKA, DLGAP5, BUB1B, and KIF20A were highly expressed in drug-resistant patients and were associated with poor prognosis. The findings suggest that AURKA, DLGAP5, BUB1B, and KIF20A are potential biomarkers linked to drug resistance and recurrence in MM. Further studies are required to elucidate the underlying molecular mechanisms and explore their potential as therapeutic targets.
多发性骨髓瘤（MM）是一种无法治愈的血液系统恶性肿瘤，化疗是主要治疗方法。然而，耐药性的产生仍然是一个重大挑战。本研究旨在确定与MM耐药相关的治疗靶点，并评估其预后意义。使用“limma”和“RobustRankAggreg”R包分析来自GSE82307、GSE146649和GSE136725的基因表达数据，以鉴定差异表达基因（DEG）。进行了功能富集分析和蛋白质-蛋白质相互作用（PPI）网络分析，并使用Cytoscape识别关键网络模块。使用来自GSE136725和MMRF CoMMpass数据库的MM患者样本验证了DEG的表达和预后相关性。共鉴定出4623个DEG，稳健秩聚合分析揭示了前20个上调基因。其中，AURKA、DLGAP5、BUB1B和KIF20A在耐药患者中高表达，且与预后不良相关。研究结果表明，AURKA、DLGAP5、BUB1B和KIF20A是与MM耐药和复发相关的潜在生物标志物。需要进一步研究以阐明潜在的分子机制，并探索它们作为治疗靶点的潜力。
