Cerebrospinal fluid methylome-based liquid biopsies for accurate malignant brain neoplasm classification
© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
BACKGROUND: Resolving the differential diagnosis between brain metastases (BM), glioblastomas (GBM), and central nervous system lymphomas (CNSL) is an important dilemma for the clinical management of the main three intra-axial brain tumor types. Currently, treatment decisions require invasive diagnostic surgical biopsies that carry risks and morbidity. This study aimed to utilize methylomes from cerebrospinal fluid (CSF), a biofluid proximal to brain tumors, for reliable non-invasive classification that addresses limitations associated with low target abundance in existing approaches.
METHODS: Binomial GLMnet classifiers of tumor type were built, in fifty iterations of 80% discovery sets, using CSF methylomes obtained from 57 BM, GBM, CNSL, and non-neoplastic control patients. Publicly-available tissue methylation profiles (N = 197) on these entities and normal brain parenchyma were used for validation and model optimization.
RESULTS: Models reliably distinguished between BM (area under receiver operating characteristic curve [AUROC] = 0.93, 95% confidence interval [CI]: 0.71-1.0), GBM (AUROC = 0.83, 95% CI: 0.63-1.0), and CNSL (AUROC = 0.91, 95% CI: 0.66-1.0) in independent 20% validation sets. For validation, CSF-based methylome signatures reliably distinguished between tumor types within external tissue samples and tumors from non-neoplastic controls in CSF and tissue. CSF methylome signals were observed to align closely with tissue signatures for each entity. An additional set of optimized CSF-based models, built using tumor-specific features present in tissue data, showed enhanced classification accuracy.
CONCLUSIONS: CSF methylomes are reliable for liquid biopsy-based classification of the major three malignant brain tumor types. We discuss how liquid biopsies may impact brain cancer management in the future by avoiding surgical risks, classifying unbiopsiable tumors, and guiding surgical planning when resection is indicated.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Neuro-oncology - 25(2023), 8 vom: 03. Aug., Seite 1452-1460 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zuccato, Jeffrey A [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers, Tumor |
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| Anmerkungen: |
Date Completed 04.08.2023 Date Revised 02.12.2023 published: Print CommentIn: Neuro Oncol. 2023 Apr 20;:. - PMID 37078878 Citation Status MEDLINE |
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| doi: |
10.1093/neuonc/noac264 |
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| funding: |
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| PPN (Katalog-ID): |
NLM349678669 |
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| 245 | 1 | 0 | |a Cerebrospinal fluid methylome-based liquid biopsies for accurate malignant brain neoplasm classification |
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| 500 | |a Date Revised 02.12.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a CommentIn: Neuro Oncol. 2023 Apr 20;:. - PMID 37078878 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a BACKGROUND: Resolving the differential diagnosis between brain metastases (BM), glioblastomas (GBM), and central nervous system lymphomas (CNSL) is an important dilemma for the clinical management of the main three intra-axial brain tumor types. Currently, treatment decisions require invasive diagnostic surgical biopsies that carry risks and morbidity. This study aimed to utilize methylomes from cerebrospinal fluid (CSF), a biofluid proximal to brain tumors, for reliable non-invasive classification that addresses limitations associated with low target abundance in existing approaches | ||
| 520 | |a METHODS: Binomial GLMnet classifiers of tumor type were built, in fifty iterations of 80% discovery sets, using CSF methylomes obtained from 57 BM, GBM, CNSL, and non-neoplastic control patients. Publicly-available tissue methylation profiles (N = 197) on these entities and normal brain parenchyma were used for validation and model optimization | ||
| 520 | |a RESULTS: Models reliably distinguished between BM (area under receiver operating characteristic curve [AUROC] = 0.93, 95% confidence interval [CI]: 0.71-1.0), GBM (AUROC = 0.83, 95% CI: 0.63-1.0), and CNSL (AUROC = 0.91, 95% CI: 0.66-1.0) in independent 20% validation sets. For validation, CSF-based methylome signatures reliably distinguished between tumor types within external tissue samples and tumors from non-neoplastic controls in CSF and tissue. CSF methylome signals were observed to align closely with tissue signatures for each entity. An additional set of optimized CSF-based models, built using tumor-specific features present in tissue data, showed enhanced classification accuracy | ||
| 520 | |a CONCLUSIONS: CSF methylomes are reliable for liquid biopsy-based classification of the major three malignant brain tumor types. We discuss how liquid biopsies may impact brain cancer management in the future by avoiding surgical risks, classifying unbiopsiable tumors, and guiding surgical planning when resection is indicated | ||
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| 650 | 4 | |a liquid biopsy | |
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| 700 | 1 | |a Patil, Vikas |e verfasserin |4 aut | |
| 700 | 1 | |a Mansouri, Sheila |e verfasserin |4 aut | |
| 700 | 1 | |a Voisin, Mathew |e verfasserin |4 aut | |
| 700 | 1 | |a Chakravarthy, Ankur |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Shu Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Nassiri, Farshad |e verfasserin |4 aut | |
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| 700 | 1 | |a De Carvalho, Daniel D |e verfasserin |4 aut | |
| 700 | 1 | |a Mansouri, Alireza |e verfasserin |4 aut | |
| 700 | 1 | |a Zadeh, Gelareh |e verfasserin |4 aut | |
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