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Whole blood transcriptional fingerprints of high-grade glioma and longitudinal tumor evolution under carbon ion radiotherapy

Purpose: To assess the value of whole blood transcriptome data from liquid biopsy (lbx) in recurrent high-grade glioma (rHGG) patients for longitudinal molecular monitoring of tumor evolution under carbon ion irradiation (CIR). Methods: Whole blood transcriptome (WBT) analysis (Illumina HumanHT-12 E...

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Main Authors: Knoll, Maximilian (Author) , Waltenberger, Maria (Author) , Furkel, Jennifer (Author) , Wirkner, Ute (Author) , Gahlawat, Aoife Ward (Author) , Dokić, Ivana (Author) , Schwager, Christian (Author) , Adeberg, Sebastian (Author) , Rieken, Stefan (Author) , Keßler, Tobias (Author) , Sahm, Felix (Author) , König, Laila (Author) , Herold-Mende, Christel (Author) , Combs, Stephanie (Author) , Debus, Jürgen (Author) , Abdollahi, Amir (Author)
Format: Article (Journal)
Language:English
Published: 28 January 2022
In: Cancers
Year: 2022, Volume: 14, Issue: 3, Pages: 1-17
ISSN:2072-6694
DOI:10.3390/cancers14030684
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers14030684
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/14/3/684
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Author Notes:Maximilian Knoll, Maria Waltenberger, Jennifer Furkel, Ute Wirkner, Aoife Ward Gahlawat, Ivana Dokic, Christian Schwager, Sebastian Adeberg, Stefan Rieken, Tobias Kessler, Felix Sahm, Laila König, Christel Herold-Mende, Stephanie E. Combs, Jürgen Debus and Amir Abdollahi
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Summary:Purpose: To assess the value of whole blood transcriptome data from liquid biopsy (lbx) in recurrent high-grade glioma (rHGG) patients for longitudinal molecular monitoring of tumor evolution under carbon ion irradiation (CIR). Methods: Whole blood transcriptome (WBT) analysis (Illumina HumanHT-12 Expression BeadChips) was performed in 14 patients with rHGG pre re-irradiation (reRT) with CIR and 3, 6 and 9 weeks post-CIR (reRT grade III:5, 36%, IV:9, 64%). Patients were irradiated with 30, 33, 36 GyRBE (n = 5, 6, 3) in 3GyRBE per fraction. Results: WTB analysis showed stable correlation with treatment characteristics and patients tumor grade, indicating a preserved tumor origin specific as well as dynamic transcriptional fingerprints of peripheral blood cells. Initial histopathologic tumor grade was indirectly associated with TMEM173 (STING), DNA-repair (ATM, POLD4) and hypoxia related genes. DNA-repair, chromatin remodeling (LIG1, SMARCD1) and immune response (FLT3LG) pathways were affected post-CIR. Longitudinal WTB fingerprints identified two distinct trajectories of rHGG evolution, characterized by differential and prognostic CRISPLD2 expression pre-CIR. Conclusions: Lbx based WTB analysis holds the potential for molecular stratification of rHGG patients and therapy monitoring. We demonstrate the feasibility of the peripheral blood transcriptome as a sentinel organ for identification of patient, tumor characteristics and CIR specific fingerprints in rHGG.
Item Description:Gesehen am 13.04.2022
Physical Description:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers14030684

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