Liquid Biopsy in Whole Blood for Identification of Gene Expression Patterns (mRNA and miRNA) Associated with Recurrence of Glioblastoma WHO CNS Grade 4

Author:

Muhtadi Razan12,Bernhardt Denise3ORCID,Multhoff Gabriele3ORCID,Hönikl Lisa4,Combs Stephanie E.356,Krieg Sandro M.47ORCID,Gempt Jens48ORCID,Meyer Bernhard4ORCID,Barsegian Vahé9,Lindemann Monika10ORCID,Kasper Mandy1,Stewart Samantha12,Port Matthias1ORCID,Abend Michael1,Diehl Christian D.356,Ostheim Patrick1

Affiliation:

1. Bundeswehr Institute of Radiobiology, 80937 Munich, Germany

2. Graduate Center of Medicine and Health, Technical University Munich, 81675 Munich, Germany

3. Department of Radiation Oncology, TUM School of Medicine and Health, Technical University of Munich (TUM), 81675 Munich, Germany

4. Department of Neurosurgery, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich (TUM), 81675 Munich, Germany

5. Deutsches Konsortium für Translational Krebsforschung (DKTK), Partner Site Munich, 80336 Munich, Germany

6. Institute of Radiation Medicine (IRM), Helmholtz Zentrum München GmbH, German Research Centre, 85764 Oberschleißheim, Germany

7. Department of Neurosurgery, University Hospital Heidelberg, Heidelberg University, 69117 Heidelberg, Germany

8. Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany

9. Institute of Nuclear Medicine, Helios Kliniken, 19055 Schwerin, Germany

10. Institute for Transfusion Medicine, University Hospital Essen, 45147 Essen, Germany

Abstract

GBM WHO CNS Grade 4 represents a major challenge for oncology due to its aggressive behavior. Conventional imaging has restrictions in detecting tumor recurrence. This prospective study aims to identify gene-based biomarkers in whole blood instead of isolating exosomes for the early detection of tumor recurrence. Blood samples (n = 33) were collected from seven GBM patients at time points before and after surgery as well as upon tumor recurrence. Four tumor tissue samples were assessed in parallel. Next-generation sequencing (NGS), including mRNA-seq and small RNA-seq, was used to analyze gene expression profiles in blood samples and tumor tissues. A novel filtering pipeline was invented to narrow down potential candidate genes. In total, between 6–93 mRNA and 1–19 small RNA candidates could be identified among the seven patients. The overlap of genes between the patients was minimal, indicating significant inter-individual variance among GBM patients. In summary, this prospective study supports the applicability of gene expression measurements in whole blood for the detection of tumor recurrence. It might provide an alternative to the challenging workflow of liquid biopsy after laborious exosome isolation from whole blood.

Publisher

MDPI AG

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