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Background <p>Gliomas, the most common brain tumors, present significant challenges in treatment, particularly glioblastoma multiforme (GBM), due to their infiltrative nature and difficulty in achieving gross total resection (GTR). Accurate assessment of surgical resection extent is critical for patient prognosis and survival. This study investigates the utility of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) as a quantitative biomarker for evaluating glioma resection extent and patient prognosis.</p> Methods <p>Next-generation sequencing (NGS) was used to profile genomic alterations in tumor DNA and CSF cfDNA obtained before and after surgery. Concordance between mutations detected in tumor tissue and CSF cfDNA was assessed. Post-operative changes in mean mutant allele frequency (MAF) and tumor mutational burden (TMB) were evaluated, and their associations with overall survival (OS) were analyzed.</p> Results <p>A high concordance rate (83.50%) exists between CSF cfDNA and tumor tissue, particularly for key somatic mutations such as <i>TERT</i>, <i>TP53</i>, <i>PTEN</i>, and <i>IDH1</i>. Post-operative cfDNA analysis shows a significant reduction in mean MAF and TMB. Apart from non-GTR and multiple lesions, patients who exhibit a ≥ 90% reduction in mean MAF or in the MAF of driver mutations post-surgery demonstrate significantly improved OS.</p> Conclusions <p>These findings suggest that CSF cfDNA effectively represents the genetic profile of gliomas and serves as a sensitive measure for surgical resection efficacy and patient prognosis, highlighting its potential as a non-invasive biomarker for enhancing post-operative management in glioma patients.</p>

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Cerebrospinal fluid cfDNA-based molecular assessment of resection extent and prognosis in glioma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月2日

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  • Jun Wu,
  • Zhiqiang Liu,
  • Tianxiang Huang,
  • Ying Wang,
  • Jian Yu,
  • Shifu Li,
  • Kang Xie,
  • Shuwen Kuang,
  • Chao Liu,
  • Longbo Zhang

摘要

Background

Gliomas, the most common brain tumors, present significant challenges in treatment, particularly glioblastoma multiforme (GBM), due to their infiltrative nature and difficulty in achieving gross total resection (GTR). Accurate assessment of surgical resection extent is critical for patient prognosis and survival. This study investigates the utility of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) as a quantitative biomarker for evaluating glioma resection extent and patient prognosis.

Methods

Next-generation sequencing (NGS) was used to profile genomic alterations in tumor DNA and CSF cfDNA obtained before and after surgery. Concordance between mutations detected in tumor tissue and CSF cfDNA was assessed. Post-operative changes in mean mutant allele frequency (MAF) and tumor mutational burden (TMB) were evaluated, and their associations with overall survival (OS) were analyzed.

Results

A high concordance rate (83.50%) exists between CSF cfDNA and tumor tissue, particularly for key somatic mutations such as TERT, TP53, PTEN, and IDH1. Post-operative cfDNA analysis shows a significant reduction in mean MAF and TMB. Apart from non-GTR and multiple lesions, patients who exhibit a ≥ 90% reduction in mean MAF or in the MAF of driver mutations post-surgery demonstrate significantly improved OS.

Conclusions

These findings suggest that CSF cfDNA effectively represents the genetic profile of gliomas and serves as a sensitive measure for surgical resection efficacy and patient prognosis, highlighting its potential as a non-invasive biomarker for enhancing post-operative management in glioma patients.