单细胞RNA-seq揭示了原发性中枢神经系统淋巴瘤细胞中与甲氨蝶呤耐药相关的多种分子特征。

IF 3.2 2区医学 Q2 CLINICAL NEUROLOGY

Journal of Neuro-Oncology Pub Date : 2025-03-01 Epub Date: 2024-12-05 DOI:10.1007/s11060-024-04893-y

Ryosuke Osako, Azusa Hayano, Atsushi Kawaguchi, Ryuya Yamanaka

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引用次数: 0

摘要

目的：甲氨蝶呤是原发性中枢神经系统淋巴瘤（PCNSL）患者最重要的单药之一。然而，25-50%导致复发，预后不良。因此，有必要研究甲氨蝶呤耐药性，以探索复发性PCNSL的补救性化疗。单细胞序列分析能够表征新的细胞类型，并提供对癌症生物学的精确理解。方法：对亲代和耐甲氨蝶呤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组。结果：我们在HKBML和TK数据集中都确定了共识模块。hla - dr - β1、hla - dq - β1和SNRPG是两个数据集中检测到的枢纽基因。选择环孢素A作为治疗甲氨蝶呤耐药细胞的候选药物。结论：本研究结果表征了培养的PCNSL细胞中甲氨蝶呤耐药相关信号通路。总的来说，这些结果可能解释了治疗反应的变化，并为PCNSL患者提供了潜在的新治疗策略。

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Single-cell RNA-seq reveals diverse molecular signatures associated with Methotrexate resistance in primary central nervous system lymphoma cells.

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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来源期刊

Journal of Neuro-Oncology 医学-临床神经学

CiteScore

6.60

自引率

7.70%

发文量

277

审稿时长

3.3 months

期刊介绍： The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.