Liquid biopsy using circulating miRNAs for the identification of recurrence-associated biomarkers in glioblastoma CNS WHO grade 4
5 affiliations
- 1Bundeswehr Institute of Radiobiology , ,
- 2Department of Radiation Oncology, TUM School of Medicine and Health , ,
- 3Department of Neurosurgery, TUM School of Medicine, Klinikum Rechts der Isar , ,
- 4Institute of Nuclear Medicine, Helios Kliniken , ,
- 5Institute for Transfusion Medicine, University Hospital , ,
Abstract
Introduction: Glioblastoma CNS WHO Grade 4 (GBM) is associated with poor prognosis and high recurrence rates despite the current therapeutic approaches. Conventional imaging, in particular Magnetic Resonance Imaging (MRI), is primarily used during follow-up to detect tumor recurrence but has limited ability to distinguish recurrence from therapy-related changes, such as tissue necrosis and postoperative scar tissue. Liquid biopsy using circulating tumor-specific serological biomarkers, such as miRNAs, provides a gene expression signature for early identification of GBM recurrence. This pilot “proof-of-concept” study investigated the potential of circulating tumor-derived miRNA in whole blood samples for early detection of tumor recurrence.
Methods: In a previous whole-transcriptome screening (NGS) study, whole-blood samples (n = 33) from seven patients and tumor biopsies (n = 4) were used to identify biomarkers. Corresponding to tumor surgery and recurrence, miRNA expression was examined in pre-surgical blood samples and tumor tissues. In whole blood, we investigated whether a pattern could be identified indicating post-surgery downregulation, consistent with reduced tumor burden, followed by a return to pre-surgery levels at recurrence. We identified 1–19 miRNA species per patient (a total of 72 miRNAs) showing this pattern. In this manuscript, we present the qRT-PCR validation results. The 45 most promising miRNAs identified by NGS study were selected and quantified using qRT-PCR. In addition, miR-21 was included as a promising candidate reported in the literature. To address challenges in miRNA normalization, five normalization strategies and unnormalized raw Ct values were compared.
Results: Two normalization approaches (median DCt normalization and unnormalized raw Ct values) showed no systematic bias. Depending on the normalization method, the agreement between NGS and qRT-PCR ranged from 23.6 to 27.9%. Although the concordance between NGS and qRT-PCR was low at the individual-patient level, qRT-PCR identified a common set of 24 miRNAs differentially regulated across patients. Notably, miR-424-3p and miR-362-5p were shared by five of seven patients, followed by miR-1307-3p and miR-22-5p , each shared by four patients. Interestingly, miR-21 did not show the predefined recurrence-associated pattern in any patient.
Discussion: Blood-based miRNA profiling may complement imaging in longitudinal monitoring of GBM patients, although clinical benefits have not been confirmed, and validation in a larger independent cohort is required.
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BibTeX
@article{muhtadi2026liquid,
title = {{Liquid biopsy using circulating miRNAs for the identification of recurrence-associated biomarkers in glioblastoma CNS WHO grade 4}},
author = {Razan Muhtadi and Christian D. Diehl and Nikolai Schmid and Gabriele Multhoff and Denise Bernhardt and Stephanie E. Combs and Lisa Hönikl and Sandro M. Krieg and Jens Gempt and Bernhard Meyer and Philipp Karschnia and Arthur Wagner and Vahe Barsegian and Monika Lindemann and Samantha Stewart and Sabrina Fischer and Patrick Ostheim and Stefan Friedrich Eder and Michael Abend},
journal = {Frontiers in oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1938611},
url = {https://europepmc.org/article/PMC/PMC13672225},
note = {CC BY},
}
RIS
TY - JOUR
TI - Liquid biopsy using circulating miRNAs for the identification of recurrence-associated biomarkers in glioblastoma CNS WHO grade 4
AU - Razan Muhtadi
AU - Christian D. Diehl
AU - Nikolai Schmid
AU - Gabriele Multhoff
AU - Denise Bernhardt
AU - Stephanie E. Combs
AU - Lisa Hönikl
AU - Sandro M. Krieg
AU - Jens Gempt
AU - Bernhard Meyer
AU - Philipp Karschnia
AU - Arthur Wagner
AU - Vahe Barsegian
AU - Monika Lindemann
AU - Samantha Stewart
AU - Sabrina Fischer
AU - Patrick Ostheim
AU - Stefan Friedrich Eder
AU - Michael Abend
PY - 2026
DA - 2026/10/02
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1938611
UR - https://europepmc.org/article/PMC/PMC13672225
AB - Introduction: Glioblastoma CNS WHO Grade 4 (GBM) is associated with poor prognosis and high recurrence rates despite the current therapeutic approaches. Conventional imaging, in particular Magnetic Resonance Imaging (MRI), is primarily used during follow-up to detect tumor recurrence but has limited ability to distinguish recurrence from therapy-related changes, such as tissue necrosis and postoperative scar tissue. Liquid biopsy using circulating tumor-specific serological biomarkers, such as miRNAs, provides a gene expression signature for early identification of GBM recurrence. This pilot “proof-of-concept” study investigated the potential of circulating tumor-derived miRNA in whole blood samples for early detection of tumor recurrence. Methods: In a previous whole-transcriptome screening (NGS) study, whole-blood samples (n = 33) from seven patients and tumor biopsies (n = 4) were used to identify biomarkers. Corresponding to tumor surgery and recurrence, miRNA expression was examined in pre-surgical blood samples and tumor tissues. In whole blood, we investigated whether a pattern could be identified indicating post-surgery downregulation, consistent with reduced tumor burden, followed by a return to pre-surgery levels at recurrence. We identified 1–19 miRNA species per patient (a total of 72 miRNAs) showing this pattern. In this manuscript, we present the qRT-PCR validation results. The 45 most promising miRNAs identified by NGS study were selected and quantified using qRT-PCR. In addition, miR-21 was included as a promising candidate reported in the literature. To address challenges in miRNA normalization, five normalization strategies and unnormalized raw Ct values were compared. Results: Two normalization approaches (median DCt normalization and unnormalized raw Ct values) showed no systematic bias. Depending on the normalization method, the agreement between NGS and qRT-PCR ranged from 23.6 to 27.9%. Although the concordance between NGS and qRT-PCR was low at the individual-patient level, qRT-PCR identified a common set of 24 miRNAs differentially regulated across patients. Notably, miR-424-3p and miR-362-5p were shared by five of seven patients, followed by miR-1307-3p and miR-22-5p , each shared by four patients. Interestingly, miR-21 did not show the predefined recurrence-associated pattern in any patient. Discussion: Blood-based miRNA profiling may complement imaging in longitudinal monitoring of GBM patients, although clinical benefits have not been confirmed, and validation in a larger independent cohort is required.
SN - 2234-943X
ER -