miR-34a-5p levels were significantly higher in GBM patients compared to healthy volunteers (AUC = 0.664, p = 0.039).
Circulating may serve as potential biomarkers for glioblastoma (GBM) diagnosis and prognosis.
All three investigated microRNAs (miR-21-5p, miR-23b-3p, and miR-34a-5p) were detectable in both healthy volunteers and GBM patients, displaying varying profiles.
Longitudinal analysis showed that miRNA levels increased at 1 and 3 months post-surgery, followed by a decrease at 6 and 12 months.
Patients with miR-34a-5p levels below the mean at diagnosis and 3 months after surgery had significantly shorter overall survival (OS) and recurrence-free survival (RFS).
OS was also significantly shorter in patients with miR-21-5p levels below the mean at 6 months after surgery.
Preliminary findings indicate the need for larger studies to validate these miRNAs as reliable prognostic biomarkers in GBM.
Simplified
Glioblastoma (GBM) is characterized by molecular heterogeneity and rapid progression. is increasingly recognised as a promising non-invasive biomarker for GBM diagnosis, prognosis and treatment monitoring. The aim of the study was to explore circulating (miRNA) as potential GBM-biomarkers. We developed droplet digital PCR (ddPCR) assays to quantify plasmatic concentrations of miR-21-5p, miR-23b-3p and miR-34a-5p both in healthy volunteers and GBM patients at diagnosis and over follow-up (1, 3, 6 and 12 months after surgery). Furthermore, we investigated the correlations between peripheral miRNA levels and clinical, neuroradiological, pathological features, extent of tumour resection, overall (OS) and recurrence-free (RFS) survivals. Our findings showed that these miRNAs were detectable in all samples, even if with different profiles, showing a similar longitudinal course characterized by a gradual increase 1 and 3 months after surgery, followed by a progressive decrease 6 and 12 months after surgery. miR-34a-5p levels were significantly higher in GBM patients compared to healthy volunteers (AUC = 0.664, p = 0.039; cut-off: 1.25 copies/µL). RFS (7.6 vs. 15.6 months, p = 0.049) and OS (8.2 vs. 24.5 months, p = 0.032) were significantly shorter in patients with miR-34a-5p levels below the mean at diagnosis and 3 months after surgery, respectively. Similarly, OS (13.3 vs. 24.4months, p = 0.024) was significantly shorter in patients with miR-21-5p levels below the mean 6 months after surgery. This study highlights the potential clinical utility of ddPCR-based quantification of plasmatic miRNAs in GBM. Longitudinal analysis revealed consistent dynamic expression patterns for all three investigated miRNAs, with miR-34a-5p and miR-21-5p emerging as potential prognostic biomarkers. Although the diagnostic performance of miR-34a-5p was intermediate and the small cohort size limited definitive conclusions, these preliminary findings support further exploration of these miRNAs as part of a multi-marker panel to enhance diagnostic and prognostic accuracy in GBM. Larger, prospective studies are required to validate these results and to elucidate the biological underpinnings of peripheral miRNA dynamics in the context of GBM pathophysiology and treatment.
Key numbers
0.664
Diagnostic for
Area under the curve for in distinguishing patients from healthy volunteers.
7.6 months vs. 15.6 months
Recurrence-free survival (RFS)
RFS for patients with levels below vs. above the mean at diagnosis.
13.3 months vs. 24.4 months
Overall survival (OS)
OS for patients with levels below vs. above the mean at 6 months post-surgery.
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Declarations. Ethics approval: This study was conducted according to the guidelines of the Declaration of Helsinki and the Good Clinical Practice (GCP) guidelines. The study protocol was approved by the Ethical Committee of the ASST Cremona (NP 32219, dated on 2 October 2019). Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: The authors affirm that human research participants provided informed consent for publication of the images. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests.
PubMed
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