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Using gene expression changes for monitoring glioblastoma WHO CNS grade 4 recurrence: Validation of NGS candidate genes via qRT-PCR.
Radiat. Res., DOI: 10.1667/rade-25-00226.1 (2026)
Glioblastoma WHO CNS Grade 4 (GBM) is associated with poor prognosis and
high recurrence rates despite the current therapeutic interventions.
Conventional imaging bears restrictions in detecting tumor recurrence
and discriminating it from tissue necrosis and post-operative scar
tissues. In a previous study, we conducted a whole-transcriptome
screening using next-generation sequencing (NGS) on whole blood samples
(n = 33) from seven patients and tumor biopsies to identify
tumor-specific gene expression patterns. This revealed downregulation
post-surgery, with a return to pre-surgery baseline levels at the time
of tumor recurrence. In the screening phase, we were able to identify
374 genes across all patients, and in this study, we aimed to validate
the most predictive genes identified in the screening phase using the
same samples with qRT-PCR (customized TaqMan array cards). A subset of
candidate genes was selected for each patient to reduce the number of
screening genes to be validated, resulting in a total of 94 genes for
validation using qRT-PCR. All genes were measured in all samples, thus
allowing a search for genes methodologically confirming the NGS
candidate genes as well as examining qRT-PCR-based gene expression
patterns, which were not captured by NGS in certain patients. Filter
criteria included a post-surgery fold change (FC) ≤ 0.6 across all or
most time points and already cited GBM-related genes. From whole blood,
total RNA was isolated, converted into cDNA, and 6,270 gene expression
measurements were performed employing custom TaqMan array cards
(qRT-PCR). We were able to successfully validate NGS candidate genes for
three patients out of seven. Differential gene expression (DGE) of both
methods was comparable for these patients (e.g., r2 = 0.76, P
< 0.001 for patient #1). Between 38–62% of NGS candidate genes per
patient could be successfully validated, but only in patients where the
screening comprised ≥20 NGS candidate genes. QRT-PCR also detected tumor
recurrence-associated expression patterns in genes that were not
captured by NGS, but 2–9-fold more candidates were observed for
NGS-selected genes. Furthermore, in a patient receiving additional
chemotherapy (CTx) during the tumor recurrence phase, a reduction in DGE
of 13 genes was observed. In another patient, DGE indicated recurrence
13 days before radiological examinations confirmed it. The evidence,
based on screening and validated, suggests a potential association, but a
coincidental link cannot be ruled out. Our findings may point to the
possible utility of gene expression measurements in peripheral whole
blood as a simplified liquid biopsy method for GBM tumor recurrence.
However, further prospective cohort studies with improved control of
sampling during clinical follow-up and radiological examinations are
needed to strengthen the presumed causality and the clinical value of
early gene expression changes as an indicator of tumor recurrence.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Candidate Gene ; Gene ; Taqman ; Gene Expression ; Gene Expression Profiling ; Reference Genes ; Glioblastoma ; Microarray
ISSN (print) / ISBN
0033-7587
e-ISSN
1938-5404
Journal
Radiation Research
Publisher
Radiation Research Society
Reviewing status
Peer reviewed
Institute(s)
Institute of Radiation Medicine (IRM)