Whole Blood Transcriptional Fingerprints of High-Grade Glioma and Longitudinal Tumor Evolution under Carbon Ion Radiotherapy

Autor: 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, Amir Abdollahi
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cancers, Vol 14, Iss 3, p 684 (2022)
Druh dokumentu: article
ISSN: 2072-6694
DOI: 10.3390/cancers14030684
Popis: 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.
Databáze: Directory of Open Access Journals