Single-cell RNA-seq reveals diverse molecular signatures associated with Methotrexate resistance in primary central nervous system lymphoma cells: scRNA Analyses of Methotrexate Resistant Brain Lymphoma Cells: R. Osako et al.

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. [ABSTRACT FROM AUTHOR]