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Open AccessArticle

A Multiplex Assay for the Stratification of Patients with Primary Central Nervous System Lymphoma Using Targeted Mass Spectrometry

1
Institute of Molecular Medicine, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany
2
Department of Neurology, Knappschaftskrankenhaus, Ruhr-University Bochum, 44789 Bochum, Germany
3
Institute of Neuropathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany
4
Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, 44789 Bochum, Germany
5
Molecular Proteomics Laboratory, Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Cancers 2020, 12(7), 1732; https://doi.org/10.3390/cancers12071732 (registering DOI)
Received: 25 May 2020 / Revised: 25 June 2020 / Accepted: 26 June 2020 / Published: 29 June 2020
(This article belongs to the Collection Application of Bioinformatics in Cancers)
Primary central nervous system lymphomas (PCNSL) account for approximately 2% to 3% of all primary brain tumors. Until now, neuropathological tumor tissue analysis, most frequently gained by stereotactic biopsy, is still the diagnostic gold standard. Here, we rigorously analyzed two independent patient cohorts comprising the clinical entities PCNSL (n = 47), secondary central nervous system lymphomas (SCNSL; n = 13), multiple sclerosis (MS, n = 23), glioma (n = 10), other tumors (n = 17) and tumor-free controls (n = 21) by proteomic approaches. In total, we identified more than 1220 proteins in the cerebrospinal fluid (CSF) and validated eight candidate biomarkers by a peptide-centric approach in an independent patient cohort (n = 63). Thus, we obtained excellent diagnostic accuracy for the stratification between PCNSL, MS and glioma patients as well as tumor-free controls for three peptides originating from the three proteins VSIG4, GPNMB4 and APOC2. The combination of all three biomarker candidates resulted in diagnostic accuracy with an area under the curve (AUC) of 0.901 (PCNSL vs. MS), AUC of 0.953 (PCNSL vs. glioma) and AUC 0.850 (PCNSL vs. tumor-free control). In summary, the determination of VSIG4, GPNMB4 and APOC2 in CSF as novel biomarkers for supporting the diagnosis of PCNSL is suggested. View Full-Text
Keywords: primary central nervous system lymphomas; secondary central nervous system lymphomas; multiple sclerosis; glioma; cerebrospinal fluid; biomarker; diagnosis; proteomics primary central nervous system lymphomas; secondary central nervous system lymphomas; multiple sclerosis; glioma; cerebrospinal fluid; biomarker; diagnosis; proteomics
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Waldera-Lupa, D.M.; Poschmann, G.; Kirchgaessler, N.; Etemad-Parishanzadeh, O.; Baberg, F.; Brocksieper, M.; Seidel, S.; Kowalski, T.; Brunn, A.; Haghikia, A.; Gold, R.; Stefanski, A.; Deckert, M.; Schlegel, U.; Stühler, K. A Multiplex Assay for the Stratification of Patients with Primary Central Nervous System Lymphoma Using Targeted Mass Spectrometry. Cancers 2020, 12, 1732.

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