Diagnostic potential of extracellular vesicles in meningioma patients
| العنوان: | Diagnostic potential of extracellular vesicles in meningioma patients |
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| المؤلفون: | Franz L Ricklefs, Cecile L Maire, Kathrin Wollmann, Lasse Dührsen, Krystian D Fita, Felix Sahm, Christel Herold-Mende, Andreas von Deimling, Katharina Kolbe, Mareike Holz, Leonie Bergmann, Marceline M Fuh, Hartmut Schlüter, Malik Alawi, Rudolph Reimer, Sven Peine, Markus Glatzel, Manfred Westphal, Katrin Lamszus |
| المصدر: | Neuro-Oncology. 24:2078-2090 |
| بيانات النشر: | Oxford University Press (OUP), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Proteomics, Extracellular Vesicles, Cancer Research, DNA Copy Number Variations, Oncology, Biomarkers, Tumor, Meningeal Neoplasms, Humans, Neurology (clinical), Meningioma, Neoplasm Proteins |
| الوصف: | Background Extracellular vesicles (EVs) play an important role in cell–cell communication, and tumor-derived EVs circulating in patient blood can serve as biomarkers. Here, we investigated the potential role of plasma EVs in meningioma patients for tumor detection and determined whether EVs secreted by meningioma cells reflect epigenetic, genomic, and proteomic alterations of original tumors. Methods EV concentrations were quantified in patient plasma (n = 46). Short-term meningioma cultures were established (n = 26) and secreted EVs were isolated. Methylation and copy number profiling was performed using 850k arrays, and mutations were identified by targeted gene panel sequencing. Differential quantitative mass spectrometry was employed for proteomic analysis. Results Levels of circulating EVs were elevated in meningioma patients compared to healthy individuals, and the plasma EV concentration correlated with malignancy grade and extent of peritumoral edema. Postoperatively, EV counts dropped to normal levels, and the magnitude of the postoperative decrease was associated with extent of tumor resection. Methylation profiling of EV-DNA allowed correct tumor classification as meningioma in all investigated cases, and accurate methylation subclass assignment in almost all cases. Copy number variations present in tumors, as well as tumor-specific mutations were faithfully reflected in meningioma EV-DNA. Proteomic EV profiling did not permit original tumor identification but revealed tumor-associated proteins that could potentially be utilized to enrich meningioma EVs from biofluids. Conclusions Elevated EV levels in meningioma patient plasma could aid in tumor diagnosis and assessment of treatment response. Meningioma EV-DNA mirrors genetic and epigenetic tumor alterations and facilitates molecular tumor classification. |
| تدمد: | 1523-5866 1522-8517 |
| DOI: | 10.1093/neuonc/noac127 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d98486cceae2adea75c0001988e36e4 https://doi.org/10.1093/neuonc/noac127 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....8d98486cceae2adea75c0001988e36e4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15235866 15228517 |
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| DOI: | 10.1093/neuonc/noac127 |