{
  "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.\n\nMethods: 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.\n\nResults: 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.\n\nDiscussion: 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.",
  "abstract_shown": true,
  "affiliations": [
    "Bundeswehr Institute of Radiobiology , ,",
    "Department of Radiation Oncology, TUM School of Medicine and Health , ,",
    "Department of Neurosurgery, TUM School of Medicine, Klinikum Rechts der Isar , ,",
    "Institute of Nuclear Medicine, Helios Kliniken , ,",
    "Institute for Transfusion Medicine, University Hospital , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Razan Muhtadi"
    },
    {
      "affs": [
        1
      ],
      "name": "Christian D. Diehl"
    },
    {
      "affs": [
        0
      ],
      "name": "Nikolai Schmid"
    },
    {
      "affs": [
        1
      ],
      "name": "Gabriele Multhoff"
    },
    {
      "affs": [
        1
      ],
      "name": "Denise Bernhardt"
    },
    {
      "affs": [
        1
      ],
      "name": "Stephanie E. Combs"
    },
    {
      "affs": [
        2
      ],
      "name": "Lisa Hönikl"
    },
    {
      "affs": [
        2
      ],
      "name": "Sandro M. Krieg"
    },
    {
      "affs": [
        2
      ],
      "name": "Jens Gempt"
    },
    {
      "affs": [
        2
      ],
      "name": "Bernhard Meyer"
    },
    {
      "affs": [
        2
      ],
      "name": "Philipp Karschnia"
    },
    {
      "affs": [
        2
      ],
      "name": "Arthur Wagner"
    },
    {
      "affs": [
        3
      ],
      "name": "Vahe Barsegian"
    },
    {
      "affs": [
        4
      ],
      "name": "Monika Lindemann"
    },
    {
      "affs": [
        0
      ],
      "name": "Samantha Stewart"
    },
    {
      "affs": [
        0
      ],
      "name": "Sabrina Fischer"
    },
    {
      "affs": [
        0
      ],
      "name": "Patrick Ostheim"
    },
    {
      "affs": [
        0
      ],
      "name": "Stefan Friedrich Eder"
    },
    {
      "affs": [
        0
      ],
      "name": "Michael Abend"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bcv1eqsxfjth8.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1938611",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672225/?tool=EBI",
  "id": "bcv1eqsxfjth8",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13672225",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "openalex",
      "1306|MicroRNA in disease regulation"
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  ],
  "openalex": "W7215090397",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672225/pdf/?tool=EBI",
  "pmcid": "PMC13672225",
  "pmid": null,
  "published": "2026-10-02",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/bcv1eqsxfjth8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13672225",
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    },
    {
      "first_seen": "2026-10-30T12:20:13Z",
      "native_id": "10.3389/fonc.2026.1938611",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1938611/full"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|MicroRNA in disease regulation",
      "subfield": "oncology"
    }
  ],
  "title": "Liquid biopsy using circulating miRNAs for the identification of recurrence-associated biomarkers in glioblastoma CNS WHO grade 4",
  "title_text": "Liquid biopsy using circulating miRNAs for the identification of recurrence-associated biomarkers in glioblastoma CNS WHO grade 4",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:13Z",
  "url": "https://research.draconitic.com/paper/bcv1eqsxfjth8",
  "venue": "Frontiers in oncology",
  "versions": []
}