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Article: Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses

TitleTargeted gene expression profiling predicts meningioma outcomes and radiotherapy responses
Authors
Issue Date9-Nov-2023
PublisherNature Research
Citation
Nature Medicine, 2023, v. 29, n. 12, p. 3067-3076 How to Cite?
Abstract

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P < 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% confidence interval 0.37 to 0.78, P = 0.0001) and suggested postoperative management could be refined for 29.8% of patients. In sum, our results identify a targeted gene expression biomarker that improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses.


Persistent Identifierhttp://hdl.handle.net/10722/340695
ISSN
2023 Impact Factor: 58.7
2023 SCImago Journal Rankings: 19.045
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChen, WC-
dc.contributor.authorChoudhury, A-
dc.contributor.authorYoungblood, MW-
dc.contributor.authorPolley, MYC-
dc.contributor.authorLucas, CHG-
dc.contributor.authorMirchia, K-
dc.contributor.authorMaas, SLN-
dc.contributor.authorSuwala, AK-
dc.contributor.authorWon, M-
dc.contributor.authorBayley, JC-
dc.contributor.authorHarmanci, AS-
dc.contributor.authorHarmanci, AO-
dc.contributor.authorKlisch, TJ-
dc.contributor.authorNguyen, MP-
dc.contributor.authorVasudevan, HN-
dc.contributor.authorMccortney, K-
dc.contributor.authorYu, TJ-
dc.contributor.authorBhave, V-
dc.contributor.authorLam, TC-
dc.contributor.authorPu, JKS-
dc.contributor.authorLi, LF-
dc.contributor.authorLeung, GKK-
dc.contributor.authorChan, JW-
dc.contributor.authorPerlow, HK-
dc.contributor.authorPalmer, JD-
dc.contributor.authorHaberler, C-
dc.contributor.authorBerghoff, AS-
dc.contributor.authorPreusser, M-
dc.contributor.authorNicolaides, TP-
dc.contributor.authorMawrin, C-
dc.contributor.authorAgnihotri, S-
dc.contributor.authorResnick, A-
dc.contributor.authorRood, BR-
dc.contributor.authorChew, J-
dc.contributor.authorYoung, JS-
dc.contributor.authorBoreta, L-
dc.contributor.authorBraunstein, SE-
dc.contributor.authorSchulte, J-
dc.contributor.authorButowski, N-
dc.contributor.authorSantagata, S-
dc.contributor.authorSpetzler, D-
dc.contributor.authorBush, NAO-
dc.contributor.authorVillanueva-Meyer, JE-
dc.contributor.authorChandler, JP-
dc.contributor.authorSolomon, DA-
dc.contributor.authorRogers, CL-
dc.contributor.authorPugh, SL-
dc.contributor.authorMehta, MP-
dc.contributor.authorSneed, PK-
dc.contributor.authorBerger, MS-
dc.contributor.authorHorbinski, CM-
dc.contributor.authorMcdermott, MW-
dc.contributor.authorPerry, A-
dc.contributor.authorBi, WL-
dc.contributor.authorPátel, AJ-
dc.contributor.authorSahm, F-
dc.contributor.authorMagill, ST-
dc.contributor.authorRaleigh, DR-
dc.date.accessioned2024-03-11T10:46:27Z-
dc.date.available2024-03-11T10:46:27Z-
dc.date.issued2023-11-09-
dc.identifier.citationNature Medicine, 2023, v. 29, n. 12, p. 3067-3076-
dc.identifier.issn1078-8956-
dc.identifier.urihttp://hdl.handle.net/10722/340695-
dc.description.abstract<p>Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (<em>N</em> = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (<em>N</em> = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, <em>P</em> < 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% confidence interval 0.37 to 0.78, <em>P</em> = 0.0001) and suggested postoperative management could be refined for 29.8% of patients. In sum, our results identify a targeted gene expression biomarker that improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses.<br></p>-
dc.languageeng-
dc.publisherNature Research-
dc.relation.ispartofNature Medicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleTargeted gene expression profiling predicts meningioma outcomes and radiotherapy responses-
dc.typeArticle-
dc.identifier.doi10.1038/s41591-023-02586-z-
dc.identifier.scopuseid_2-s2.0-85178447510-
dc.identifier.volume29-
dc.identifier.issue12-
dc.identifier.spage3067-
dc.identifier.epage3076-
dc.identifier.eissn1546-170X-
dc.identifier.isiWOS:001113405000001-
dc.identifier.issnl1078-8956-

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