Osako Ryosuke, Hayano Azusa, Kawaguchi Atsushi, Yamanaka Ryuya
Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Department of Cardiovascular Medicine, Saga University, Saga, Japan.
J Neurooncol. 2025 Mar;172(1):163-173. doi: 10.1007/s11060-024-04893-y. Epub 2024 Dec 5.
Methotrexate is one of the most essential single agents in patients with primary central nervous system lymphoma (PCNSL). However, 25-50% result in relapse with a poor prognosis. Therefore, studies on methotrexate resistance are warranted to explore salvage chemotherapy for recurrent PCNSL. Single-cell sequence analysis enables the characterization of novel cell types and provides a precise understanding of cancer biology.
Single-cell sequence analysis of parental and methotrexate-resistant PCNSL cells was performed. We used a Weighted Gene Co-expression Network Analysis to identify groups of significantly connected genes.
We identified consensus modules in both the HKBML and TK datasets. HLA-DRβ1, HLA-DQβ1,and SNRPG were hub genes those detected in both datasets revealed by network analysis. Cyclosporine A was selected as the candidate drug for treating methotrexate-resistant cells.
The results of the present study characterized the methotrexate resistance-related signaling pathways in cultured PCNSL cells. Overall, these results may account for variations in treatment responses and lead potential novel therapeutic strategies for patients with PCNSL.
甲氨蝶呤是原发性中枢神经系统淋巴瘤（PCNSL）患者最重要的单一药物之一。然而，25%-50%的患者会复发，预后较差。因此，有必要开展关于甲氨蝶呤耐药性的研究，以探索复发性PCNSL的挽救化疗方案。单细胞序列分析能够对新型细胞类型进行表征，并提供对癌症生物学的精确理解。
对亲本及甲氨蝶呤耐药的PCNSL细胞进行单细胞序列分析。我们使用加权基因共表达网络分析来识别显著连接的基因群。
我们在HKBML和TK数据集中均识别出了共表达模块。网络分析显示，HLA-DRβ1、HLA-DQβ1和SNRPG是在两个数据集中均检测到的核心基因。环孢素A被选为治疗甲氨蝶呤耐药细胞的候选药物。
本研究结果表征了培养的PCNSL细胞中与甲氨蝶呤耐药相关的信号通路。总体而言，这些结果可能解释了治疗反应的差异，并为PCNSL患者带来潜在的新型治疗策略。
