Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses.
William C ChenAbrar ChoudhuryMark W YoungbloodMei-Yin C PolleyCalixto-Hope G LucasKanish MirchiaSybren L N MaasAbigail K SuwalaMinhee WonJames C BayleyAkdes S HarmanciArif HarmanciTiemo J KlischMinh P NguyenHarish N VasudevanKathleen McCortneyTheresa J YuVarun BhaveTai-Chung LamJenny Kan-Suen PuLai-Fung LiGilberto Ka Kit LeungJason W ChanHaley K PerlowJoshua David PalmerChristine HaberlerAnna Sophie BerghoffMatthias PreusserTheodore P NicolaidesChristian MawrinSameer AgnihotriAdam ResnickBrian R RoodJessica ChewJacob S YoungLauren BoretaSteve E BraunsteinJessica SchulteNicholas ButowskiSandro SantagataDavid SpetzlerNancy Ann Oberheim BushJavier E Villanueva-MeyerJames P ChandlerDavid A SolomonC Leland RogersStephanie L PughMinesh P MehtaPenny K SneedMitchel S BergerCraig M HorbinskiMichael W McDermottArie PerryWenya Linda BiAkash J PatelFelix SahmStephen T MagillDavid R RaleighPublished in: Nature medicine (2023)
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.
Keyphrases
- gene expression
- early stage
- dna methylation
- locally advanced
- patients undergoing
- clinical trial
- radiation therapy
- radiation induced
- optic nerve
- end stage renal disease
- healthcare
- cancer therapy
- chronic kidney disease
- randomized controlled trial
- free survival
- minimally invasive
- palliative care
- newly diagnosed
- small molecule
- single cell
- study protocol
- high throughput
- adipose tissue
- rectal cancer
- metabolic syndrome
- open label
- health insurance
- peritoneal dialysis
- insulin resistance
- pain management
- acute coronary syndrome
- combination therapy
- skeletal muscle
- replacement therapy
- chronic pain
- percutaneous coronary intervention
- phase ii