TY - JOUR
T1 - New biomarkers for the diagnosis of primary central nervous system lymphoma in CSF
T2 - A multicenter retrospective cohort study
AU - Van Rooij, Josephus L.M.
AU - Wessels, Peter H.
AU - Delemarre, Eveline M.
AU - Meek, Bob
AU - Ruven, Henk J.T.
AU - Seute, Tatjana
AU - Minnema, Monique C.
AU - Nierkens, Stefan
AU - Snijders, Tom J.
N1 - © The Author(s) 2025. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
PY - 2025/1/1
Y1 - 2025/1/1
N2 - 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 183 protein markers in a small CSF volume (1 μl). To validate the potential identified biomarkers, a second quantitative analysis was performed in a subgroup with a bead-based multiplex immuno-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 < .05) between PCNSL patients and controls. After correction for multiple testing, 6 markers remained significant. The quantitative analysis confirmed significant differences (
P < .05) for 3 markers: CXCL10, programmed cell death protein 1 (PDCD1), and FAS natural ligand.
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.
AB - 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 183 protein markers in a small CSF volume (1 μl). To validate the potential identified biomarkers, a second quantitative analysis was performed in a subgroup with a bead-based multiplex immuno-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 < .05) between PCNSL patients and controls. After correction for multiple testing, 6 markers remained significant. The quantitative analysis confirmed significant differences (
P < .05) for 3 markers: CXCL10, programmed cell death protein 1 (PDCD1), and FAS natural ligand.
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.
KW - CSF biomarkers
KW - CXCL10
KW - FASLG
KW - PDCD1
KW - primary CNS lymphoma
UR - https://www.scopus.com/pages/publications/105026072094
UR - https://www.mendeley.com/catalogue/8b085ce0-81f0-3cb3-8bc0-8b16b06b3fff/
U2 - 10.1093/noajnl/vdaf208
DO - 10.1093/noajnl/vdaf208
M3 - Article
C2 - 41473751
AN - SCOPUS:105026072094
SN - 2632-2498
VL - 7
JO - Neuro-Oncology Advances
JF - Neuro-Oncology Advances
IS - 1
M1 - vdaf208
ER -