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Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses

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 meningio...

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Main Authors: Chen, William C. (Author) , Choudhury, Abrar (Author) , Youngblood, Mark W. (Author) , Polley, Mei-Yin C. (Author) , Lucas, Calixto-Hope G. (Author) , Mirchia, Kanish (Author) , Maas, Sybren L. N. (Author) , Suwala, Abigail Kora (Author) , Won, Minhee (Author) , Bayley, James C. (Author) , Harmanci, Akdes S. (Author) , Harmanci, Arif O. (Author) , Klisch, Tiemo (Author) , Nguyen, Minh P. (Author) , Vasudevan, Harish N. (Author) , McCortney, Kathleen (Author) , Yu, Theresa J. (Author) , Bhave, Varun (Author) , Lam, Tai-Chung (Author) , Pu, Jenny Kan-Suen (Author) , Li, Lai-Fung (Author) , Leung, Gilberto Ka-Kit (Author) , Chan, Jason W. (Author) , Perlow, Haley K. (Author) , Palmer, Joshua D. (Author) , Haberler, Christine (Author) , Bergmeister-Berghoff, Anna Sophie (Author) , Preusser, Matthias (Author) , Nicolaides, Theodore P. (Author) , Mawrin, Christian (Author) , Agnihotri, Sameer (Author) , Resnick, Adam (Author) , Rood, Brian R. (Author) , Chew, Jessica (Author) , Young, Jacob S. (Author) , Boreta, Lauren (Author) , Braunstein, Steve E. (Author) , Schulte, Jessica (Author) , Butowski, Nicholas (Author) , Santagata, Sandro (Author) , Spetzler, David (Author) , Bush, Nancy Ann Oberheim (Author) , Villanueva-Meyer, Javier E. (Author) , Chandler, James P. (Author) , Solomon, David (Author) , Rogers, C. Leland (Author) , Pugh, Stephanie L. (Author) , Mehta, Minesh P. (Author) , Sneed, Penny K. (Author) , Berger, Mitchel S. (Author) , Horbinski, Craig M. (Author) , McDermott, Michael W. (Author) , Perry, Arie (Author) , Bi, Wenya Linda (Author) , Patel, Akash J. (Author) , Sahm, Felix (Author) , Magill, Stephen T. (Author) , Raleigh, David R. (Author)
Format: Article (Journal)
Language:English
Published: 09 November 2023
In: Nature medicine
Year: 2023, Volume: 29, Issue: 12, Pages: 3067-3076
ISSN:1546-170X
DOI:10.1038/s41591-023-02586-z
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41591-023-02586-z
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41591-023-02586-z
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Author Notes:William C. Chen, Abrar Choudhury, Mark W. Youngblood, Mei-Yin C. Polley, Calixto-Hope G. Lucas, Kanish Mirchia, Sybren L. N. Maas, Abigail K. Suwala, Minhee Won, James C. Bayley, Akdes S. Harmanci, Arif O. Harmanci, Tiemo J. Klisch, Minh P. Nguyen, Harish N. Vasudevan, Kathleen McCortney, Theresa J. Yu, Varun Bhave, Tai-Chung Lam, Jenny Kan-Suen Pu, Lai-Fung Li, Gilberto Ka-Kit Leung, Jason W. Chan, Haley K. Perlow, Joshua D. Palmer, Christine Haberler, Anna S. Berghoff, Matthias Preusser, Theodore P. Nicolaides, Christian Mawrin, Sameer Agnihotri, Adam Resnick, Brian R. Rood, Jessica Chew, Jacob S. Young, Lauren Boreta, Steve E. Braunstein, Jessica Schulte, Nicholas Butowski, Sandro Santagata, David Spetzler, Nancy Ann Oberheim Bush, Javier E. Villanueva-Meyer, James P. Chandler, David A. Solomon, C. Leland Rogers, Stephanie L. Pugh, Minesh P. Mehta, Penny K. Sneed, Mitchel S. Berger, Craig M. Horbinski, Michael W. McDermott, Arie Perry, Wenya Linda Bi, Akash J. Patel, Felix Sahm, Stephen T. Magill & David R. Raleigh
Description
Summary: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.
Item Description:Gesehen am 09.02.2024
Physical Description:Online Resource
ISSN:1546-170X
DOI:10.1038/s41591-023-02586-z

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