A Multiplex Assay for the Stratification of Patients with Primary Central Nervous System Lymphoma Using Targeted Mass Spectrometry
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 pati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/7/1732 |
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| author | Daniel M. Waldera-Lupa Gereon Poschmann Nina Kirchgaessler Omid Etemad-Parishanzadeh Falk Baberg Mareike Brocksieper Sabine Seidel Thomas Kowalski Anna Brunn Aiden Haghikia Ralf Gold Anja Stefanski Martina Deckert Uwe Schlegel Kai Stühler |
| author_facet | Daniel M. Waldera-Lupa Gereon Poschmann Nina Kirchgaessler Omid Etemad-Parishanzadeh Falk Baberg Mareike Brocksieper Sabine Seidel Thomas Kowalski Anna Brunn Aiden Haghikia Ralf Gold Anja Stefanski Martina Deckert Uwe Schlegel Kai Stühler |
| author_sort | Daniel M. Waldera-Lupa |
| collection | DOAJ |
| description | 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 (<i>n</i> = 47), secondary central nervous system lymphomas (SCNSL; <i>n</i> = 13), multiple sclerosis (MS, <i>n</i> = 23), glioma (<i>n</i> = 10), other tumors (<i>n</i> = 17) and tumor-free controls (<i>n</i> = 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 (<i>n</i> = 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. |
| first_indexed | 2024-03-10T18:48:46Z |
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| id | doaj.art-ced6b53f3a8541f39b502bf26c4b154a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:48:46Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ced6b53f3a8541f39b502bf26c4b154a2023-11-20T05:20:18ZengMDPI AGCancers2072-66942020-06-01127173210.3390/cancers12071732A Multiplex Assay for the Stratification of Patients with Primary Central Nervous System Lymphoma Using Targeted Mass SpectrometryDaniel M. Waldera-Lupa0Gereon Poschmann1Nina Kirchgaessler2Omid Etemad-Parishanzadeh3Falk Baberg4Mareike Brocksieper5Sabine Seidel6Thomas Kowalski7Anna Brunn8Aiden Haghikia9Ralf Gold10Anja Stefanski11Martina Deckert12Uwe Schlegel13Kai Stühler14Institute of Molecular Medicine, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyInstitute of Molecular Medicine, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyInstitute of Molecular Medicine, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyInstitute of Molecular Medicine, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyInstitute of Molecular Medicine, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyInstitute of Molecular Medicine, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyDepartment of Neurology, Knappschaftskrankenhaus, Ruhr-University Bochum, 44789 Bochum, GermanyDepartment of Neurology, Knappschaftskrankenhaus, Ruhr-University Bochum, 44789 Bochum, GermanyInstitute of Neuropathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyDepartment of Neurology, St. Josef-Hospital, Ruhr-University Bochum, 44789 Bochum, GermanyDepartment of Neurology, St. Josef-Hospital, Ruhr-University Bochum, 44789 Bochum, GermanyMolecular Proteomics Laboratory, Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Neuropathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyDepartment of Neurology, Knappschaftskrankenhaus, Ruhr-University Bochum, 44789 Bochum, GermanyInstitute of Molecular Medicine, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, GermanyPrimary 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 (<i>n</i> = 47), secondary central nervous system lymphomas (SCNSL; <i>n</i> = 13), multiple sclerosis (MS, <i>n</i> = 23), glioma (<i>n</i> = 10), other tumors (<i>n</i> = 17) and tumor-free controls (<i>n</i> = 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 (<i>n</i> = 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.https://www.mdpi.com/2072-6694/12/7/1732primary central nervous system lymphomassecondary central nervous system lymphomasmultiple sclerosisgliomacerebrospinal fluidbiomarker |
| spellingShingle | Daniel M. Waldera-Lupa Gereon Poschmann Nina Kirchgaessler Omid Etemad-Parishanzadeh Falk Baberg Mareike Brocksieper Sabine Seidel Thomas Kowalski Anna Brunn Aiden Haghikia Ralf Gold Anja Stefanski Martina Deckert Uwe Schlegel Kai Stühler A Multiplex Assay for the Stratification of Patients with Primary Central Nervous System Lymphoma Using Targeted Mass Spectrometry Cancers primary central nervous system lymphomas secondary central nervous system lymphomas multiple sclerosis glioma cerebrospinal fluid biomarker |
| title | A Multiplex Assay for the Stratification of Patients with Primary Central Nervous System Lymphoma Using Targeted Mass Spectrometry |
| title_full | A Multiplex Assay for the Stratification of Patients with Primary Central Nervous System Lymphoma Using Targeted Mass Spectrometry |
| title_fullStr | A Multiplex Assay for the Stratification of Patients with Primary Central Nervous System Lymphoma Using Targeted Mass Spectrometry |
| title_full_unstemmed | A Multiplex Assay for the Stratification of Patients with Primary Central Nervous System Lymphoma Using Targeted Mass Spectrometry |
| title_short | A Multiplex Assay for the Stratification of Patients with Primary Central Nervous System Lymphoma Using Targeted Mass Spectrometry |
| title_sort | multiplex assay for the stratification of patients with primary central nervous system lymphoma using targeted mass spectrometry |
| topic | primary central nervous system lymphomas secondary central nervous system lymphomas multiple sclerosis glioma cerebrospinal fluid biomarker |
| url | https://www.mdpi.com/2072-6694/12/7/1732 |
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