New biomarkers for the diagnosis of primary Central nervous system lymphoma in CSF: a multicenter retrospective cohort study
Neuro-Oncology Advances, 2025
van Rooij J., Wessels P., Delemarre E., Meek B., Ruven H., Seute T., Minnema M., Nierkens S., Snijders T.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Oncology | Patient Stratification | CSF |  Olink Target 96 |
Abstract
Background
Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma. Diagnosis usually requires a brain biopsy, which is associated with complications and delay of diagnosis. Cerebrospinal fluid (CSF) analysis can provide a diagnosis without the need for a biopsy, but only in a minority of PCNSL patients. The aim of this study is to identify new potential biomarkers in CSF for patients with clinical suspicion of PCNSL, to improve the diagnostic yield of CSF analysis.
Methods
CSF samples were analyzed from a retrospective cohort that included patients with clinical suspicion of PCNSL. First-step analysis consisted of targeted multiplex biomarker analysis with use of a proximity extension assay (Olink®), allowing the simultaneous analysis of relative expression levels of 184 protein markers in a small CSF volume (1μl). To validate the potential identified biomarkers, a second quantitative analysis was performed in a subgroup with a bead-based multiplex immune-assay.
Results
We included 74 patients, of whom 11 patients (15%) were diagnosed with PCNSL. In the primary analysis, 30 markers showed significant differences (p < 0.05) between PCNSL patients and controls. After correction for multiple testing, 6 markers remained significant. The quantitative analysis confirmed significant differences (p < 0.05) for 3 markers: CXCL10, programmed cell death protein 1 (PDCD1) and FAS natural ligand (FASLG).
Conclusions
We identified a panel of novel potential diagnostic markers in CSF for the diagnosis of PCNSL and confirmed the value of several known markers. The diagnostic value of these markers will be validated in a multicenter prospective study.