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

  • J Neurooncol. 2024 Dec 5. doi: 10.1007/s11060-024-04893-y.
Ryosuke Osako  1  2 ,  Azusa Hayano  3 ,  Atsushi Kawaguchi  1 ,  Ryuya Yamanaka  4
Affiliations
  • 1. Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, Saga, Japan.
  • 2. Department of Cardiovascular Medicine, Saga University, Saga, Japan.
  • 3. Laboratory of Molecular Target Therapy for Cancer, Graduate School for Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyoku, Kyoto, 602-8566, Japan.
  • 4. Laboratory of Molecular Target Therapy for Cancer, Graduate School for Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyoku, Kyoto, 602-8566, Japan. [email protected].
PMID: 39636551 DOI: 10.1007/s11060-024-04893-y
Abstract

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.

Keywords
Cyclosporine A; Methotrexate resistance; Primary central nervous system lymphoma; Single-cell transcriptome analyses.
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