靶向基因表达谱可预测脑膜瘤结果和放射治疗反应。
Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses.
发表日期：2023 Nov 09
作者：
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 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
来源：
NATURE MEDICINE
摘要：
手术是脑膜瘤（最常见的原发性颅内肿瘤）的主要治疗方法，但需要改进脑膜瘤风险分层，并且术后放疗的适应症存在争议。在这里，我们开发了一种靶向基因表达生物标志物，可以预测脑膜瘤的结果和放射治疗反应。利用 173 个脑膜瘤的发现队列，我们开发了 34 个基因表达风险评分，并对来自 3 大洲 12 个机构的独立脑膜瘤 (N = 1856) 进行了该生物标志物的临床和分析验证，其中包括来自前瞻性临床试验的 103 个脑膜瘤。与临床验证队列中测试的所有其他系统 (N = 9) 相比，基因表达生物标志物改善了对局部复发（5 年曲线下面积 [AUC] 0.81）和总体生存（5 年 AUC 0.80）结果的辨别力。与世界卫生组织 2021 年护理标准相比，局部复发的曲线下面积增加了 0.11（95% 置信区间 [CI] 0.07-0.17，P<0.001）。基因表达生物标志物识别出脑膜瘤受益于术后放疗（风险比 0.54，95% CI 0.37-0.78，P = 0.0001），并建议可以对 29.8% 的患者进行精细的术后管理。总之，我们的结果确定了一种靶向基因表达生物标志物，可以改善对脑膜瘤结果的辨别，包括预测术后放疗反应。© 2023。作者，获得 Springer Nature America, Inc. 的独家许可。
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 = 1856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared to 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 area under the curve compared to the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval [CI] 0.07-0.17, P < 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% CI 0.37-0.78, 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.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.