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

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.