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Muhtadi, R.* ; Diehl, C. ; Schmid, N.* ; Multhoff, G.* ; Bernhardt, D.* ; Combs, S.E. ; Hönikl, L.S.* ; Krieg, S.M.* ; Gempt, J.* ; Meyer, B.* ; Karschnia, P.* ; Wagner, A.* ; Barsegian, V.* ; Lindemann, M.* ; Stewart, S.* ; Fischer, S.* ; Ostheim, P.* ; Eder, S.F.* ; Abend, M.*

Liquid biopsy using circulating miRNAs for the identification of recurrence-associated biomarkers in glioblastoma CNS WHO grade 4.

Front. Oncol. 16:1938611 (2026)
Publ. Version/Full Text DOI
Open Access Gold
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Keywords gene expression; glioblastoma CNS WHO grade 4; liquid biopsy; magnetic resonance imaging (MRI); qRT-PCR; Gene-expression Signature; Cerebrospinal-fluid; Early Prediction; Tumor; Diagnosis; Temozolomide; Radiation
ISSN (print) / ISBN 2234-943X
e-ISSN 2234-943X
Journal Frontiers in Oncology
Quellenangaben Volume: 16, Issue: , Pages: , Article Number: 1938611 Supplement: ,
Publisher Frontiers
Publishing Place Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Reviewing status Peer reviewed
Institute(s) Institute of Radiation Medicine (IRM)
Grants Fridericus Stiftung
German Ministry of Defense