Abstract
Primary central nervous system lymphoma (PCNSL) is associated with cerebral inflammation characterized by elevated neutrophils, monocytes, platelets, and lymphocytes. However, the comprehensive profile of inflammation-related molecules in PCNSL remains unclear. In this study, we conducted proteomic analysis of PCNSL tissue compared with normal brain to identify factors influencing neuroinflammation and potential therapeutic targets. In contrast to the general elevation of inflammatory molecules, cystatin C (Cyst C) showed markedly reduced expression. This result was confirmed by western blotting and mRNA analysis. Immunohistochemistry revealed widespread Cyst C positivity in glial cells of the normal brain, whereas PCNSL tissue was dominated by Cyst C-negative B cells. To further investigate its role, cultured PCNSL cells were treated with recombinant human Cyst C. Treatment reduced viable cell counts in a dose- and time-dependent manner over 4 days without inducing cell death, indicating inhibition of cell division. Immunohistochemistry demonstrated that Cyst C increased p21 expression and decreased cyclin-dependent kinase 1 and Cyclin B. These findings identify Cyst C as a regulator of PCNSL cell division, highlighting it as a potential therapeutic target.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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The authors thank Alfredo Shimabuku for his valuable advice regarding the research described in this manuscript.
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Hiroshi Koyama conceived and coordinated the study, performed material preparation, data collection, and analysis, and wrote the first draft of the manuscript. Izumi Yamaguchi and Noriya Enomoto contributed to experimental design and provided technical support for data acquisition. Taku Matsuda and Hiroshi Kagusa assisted with data interpretation and statistical analysis. Kohei Nakajima and Keiko T. Kitazato contributed to clinical data evaluation and manuscript revision. Yasushi Takagi supervised the overall project and provided critical feedback on all manuscript drafts. All authors read and approved the final version of the manuscript.
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This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethics approval was granted by the Ethics Committee of Tokushima University Hospital (Approval No.3649–2).
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Koyama, H., Nakajima, K., Yamaguchi, I. et al. Cystatin C regulates cell division in primary central nervous system lymphoma. Sci Rep (2026). https://doi.org/10.1038/s41598-026-44039-w
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DOI: https://doi.org/10.1038/s41598-026-44039-w
