Wu Jinsong, Wu Shuai, Cao Dandan, Xiong Zhang, Zhang Jianhua, Zou Yourui, Wu Zanyi, Nie Yanli, Luo Chen, Yao Ye, Song Yanyan, Jiao Yuchen, Chen Hong, Ma Hui, Kang Dezhi, Mao Ying, Yan Hai
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China.
National Center for Neurological Disorders, Shanghai, 200052, China.
BMC Med. 2025 Jun 2;23(1):325. doi: 10.1186/s12916-025-04124-9.
Molecular biomarkers have become an essential part of the diagnosis of adult-type diffuse glioma. Still, complex detection methods and long-term turnaround for these biomarkers hinder integrated diagnosis in clinical practice. We hypothesized that IDH and TERT promoter (TERTp) mutations play similar roles in accurately classifying adult-type diffuse glioma compared to the complicated WHO CNS5-recommended biomarkers, and the detection of IDH and TERTp mutations should be the first layer in clinical practice.
We propose a novel layered diagnostic scheme for adult-type diffuse gliomas, with IDH and TERTp mutation detection as the initial layer. We also developed a rapid intraoperative testing technology capable of detecting TERTp and IDH mutations within 35 min. This study involved both a retrospective cohort and a prospective multicenter diagnostic test. The diagnostic accuracy of the layered approach was evaluated using sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC), with a 95% confidence interval.
In retrospective cohort, the TERTp mutation demonstrated comparable statistical power to 1p/19q codeletion in distinguishing oligodendrogliomas from astrocytomas (κ = 0.96, P < 0.001). Additionally, 91.8% of glioblastomas with either EGFR amplification or + 7/-10 exhibited TERTp mutations. In the prospective application of the layered diagnostic scheme and rapid testing, 223 gliomas and 2 non-gliomas (76.5%) were accurately classified intraoperatively. With the addition of postoperative permanent section analysis, 249 gliomas and 24 non-gliomas (92.9%) were correctly classified following the detection of the first-layer biomarkers.
The proposed layered diagnostic scheme offers a rapid and accurate means of classifying adult-type diffuse gliomas, facilitating the broader use of molecular classification. It expands its applicability from postoperative to intraoperative settings for the majority of patients, enhancing diagnostic efficiency and accuracy.
ClinicalTrials.gov NCT04924127, NCT04904419.
分子生物标志物已成为成人型弥漫性胶质瘤诊断的重要组成部分。然而，这些生物标志物复杂的检测方法和较长的周转时间阻碍了临床实践中的综合诊断。我们假设，与世界卫生组织（WHO）中枢神经系统肿瘤分类第5版（CNS5）推荐的复杂生物标志物相比，异柠檬酸脱氢酶（IDH）和端粒酶逆转录酶启动子（TERTp）突变在准确分类成人型弥漫性胶质瘤中发挥相似作用，并且IDH和TERTp突变检测应成为临床实践中的第一层检测。
我们提出了一种针对成人型弥漫性胶质瘤的新型分层诊断方案，将IDH和TERTp突变检测作为初始层。我们还开发了一种快速术中检测技术，能够在35分钟内检测TERTp和IDH突变。本研究包括回顾性队列研究和前瞻性多中心诊断试验。使用灵敏度、特异性和受试者工作特征曲线下面积（AUC）及95%置信区间评估分层方法的诊断准确性。
在回顾性队列中，TERTp突变在区分少突胶质细胞瘤和星形细胞瘤方面显示出与1p/19q共缺失相当的统计学效力（κ = 0.96，P < 0.001）。此外，91.8%的伴有表皮生长因子受体（EGFR）扩增或+7/-10的胶质母细胞瘤存在TERTp突变。在分层诊断方案和快速检测的前瞻性应用中，术中准确分类了223例胶质瘤和2例非胶质瘤（76.5%）。加上术后永久切片分析，在检测第一层生物标志物后，正确分类了249例胶质瘤和24例非胶质瘤（92.9%）。
所提出的分层诊断方案为成人型弥漫性胶质瘤的分类提供了一种快速准确的方法，有助于更广泛地应用分子分类。它将其适用性从大多数患者的术后扩展到术中，提高了诊断效率和准确性。
ClinicalTrials.gov NCT04924127，NCT04904419。
