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利用太赫兹吸收光谱法在胶质母细胞瘤中快速诊断TERT启动子突变

Rapid diagnosis of TERT promoter mutation using Terahertz absorption spectroscopy in glioblastoma.

作者信息

Sun Zhiyan, Du Minghui, Wu Xianhao, Tao Rui, Sun Peiyuan, Zheng Shaowen, Zhang Zhaohui, Zhou Dabiao, Zhao Xiaoyan, Yang Pei

机构信息

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

出版信息

Sci Rep. 2025 May 27;15(1):18480. doi: 10.1038/s41598-025-03161-x.

DOI:10.1038/s41598-025-03161-x
PMID:40425623
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12117072/
Abstract

Glioblastoma (GBM) is a highly aggressive brain tumor with poor outcomes and limited treatment options. The telomerase reverse transcriptase (TERT) promoter mutation, one of the key biomarkers in GBM, is linked to tumor progression and prognosis. This study employed terahertz time-domain spectroscopy (THz-TDS) to analyze frozen GBM tissue sections, extracting six spectral features: absorption coefficient, dielectric loss factor, dielectric constant, extinction coefficient, refractive index, and dielectric loss tangent. LASSO regression was employed for feature selection, and then principal component analysis (PCA) was applied to minimize inter-feature correlations. A Random Forest classifier built on these features successfully predicted TERT mutation status, achieving an area under the receiver operating characteristic curve (AUC) of 0.908 in the validation set. Our findings demonstrate that THz spectroscopy, coupled with machine learning, can identify molecular differences associated with TERT mutations, supporting its potential as a rapid, intraoperative diagnostic tool for personalized GBM treatment. This approach could enhance surgical decision-making and optimize patient outcomes through precise, real-time molecular diagnostics.

摘要

胶质母细胞瘤(GBM)是一种侵袭性很强的脑肿瘤,预后较差且治疗选择有限。端粒酶逆转录酶(TERT)启动子突变是GBM的关键生物标志物之一,与肿瘤进展和预后相关。本研究采用太赫兹时域光谱(THz-TDS)分析冷冻的GBM组织切片,提取了六个光谱特征:吸收系数、介电损耗因子、介电常数、消光系数、折射率和介电损耗角正切。采用LASSO回归进行特征选择,然后应用主成分分析(PCA)来最小化特征间的相关性。基于这些特征构建的随机森林分类器成功预测了TERT突变状态,在验证集中的受试者工作特征曲线下面积(AUC)达到0.908。我们的研究结果表明,太赫兹光谱结合机器学习可以识别与TERT突变相关的分子差异,支持其作为一种快速的术中诊断工具用于个性化GBM治疗的潜力。这种方法可以通过精确的实时分子诊断来加强手术决策并优化患者预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b662/12117072/f50ba1811312/41598_2025_3161_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b662/12117072/4de8c99a5234/41598_2025_3161_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b662/12117072/086595fe19a8/41598_2025_3161_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b662/12117072/69cff6082a13/41598_2025_3161_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b662/12117072/b3fdd3af8d4a/41598_2025_3161_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b662/12117072/32ba6383375a/41598_2025_3161_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b662/12117072/f50ba1811312/41598_2025_3161_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b662/12117072/4de8c99a5234/41598_2025_3161_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b662/12117072/086595fe19a8/41598_2025_3161_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b662/12117072/69cff6082a13/41598_2025_3161_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b662/12117072/b3fdd3af8d4a/41598_2025_3161_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b662/12117072/32ba6383375a/41598_2025_3161_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b662/12117072/f50ba1811312/41598_2025_3161_Fig6_HTML.jpg

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本文引用的文献

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Ann Clin Transl Neurol. 2024 Aug;11(8):2176-2187. doi: 10.1002/acn3.52138. Epub 2024 Jun 24.
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Biomedical application of terahertz imaging technology: a narrative review.太赫兹成像技术的生物医学应用:一篇叙述性综述。
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MRI radiomics model for predicting TERT promoter mutation status in glioblastoma.
MRI 放射组学模型预测胶质母细胞瘤 TERT 启动子突变状态。
Brain Behav. 2023 Dec;13(12):e3324. doi: 10.1002/brb3.3324. Epub 2023 Dec 6.
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Comprehensive clinical assays for molecular diagnostics of gliomas: the current state and future prospects.神经胶质瘤分子诊断的综合临床检测:现状与未来前景
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Peritumoral Radiomics for Identification of Telomerase Reverse Transcriptase Promoter Mutation in Patients With Glioblastoma Based on Preoperative MRI.基于术前 MRI 的胶质母细胞瘤患者端粒酶逆转录酶启动子突变的瘤周放射组学识别
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