超早期低级别胶质瘤:如何通过术中分子诊断界定和区分这些容易误诊的胶质瘤?

IF 4.8 1区 医学 Q1 NEUROSCIENCES
Zhe Han, Qingtong Wang, Jia Li, Huizhong Chi, Caizhi Ma, Deze Jia, Mei Qi, Xueen Li, Kailiang Zhang, Zichao Feng, Hao Xue, Gang Li
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引用次数: 0

摘要

背景:一些低级别胶质瘤(LGG)在手术中很难从形态学上与胶质细胞增生或炎症改变区分开来,导致误诊的风险很高。区分两者对于手术决策至关重要。我们将这些危重病例定义为 "超早期低级别胶质瘤(UES-LGG)":我们分析了 13 例在手术中被诊断为 "胶质病变 "或 "炎症改变 "的病例中的 11 例,这些病例的异柠檬酸脱氢酶(IDH)检测结果呈阳性。此外,我们还对 35 例手术中被诊断为 LGG 的样本进行了 qRT-PCR 检测,并在有效循环阈值范围内分析了其 DNA 含量,以推断 UES-LGG 与 LGG 之间的临界值。我们使用 5 份标准化样本进行了实验,以推断手术中 UES-LGG 准确检测的有限范围:在对 11 个样本和 35 个样本的对比分析中发现,虽然两组样本的平均 DNA 检测浓度没有显著差异(159.36 ± 83.3 ng/μL 和 146.83 ± 122.43 ng/μL),但阳性突变的检测临界值却存在明显的统计学差异(分别为 31.78 ± 1.14 和 26.14 ± 2.69)。这表明,IDH 突变率可作为区分两组的指标。随后,从标准化的 IDH 突变样本中提取 DNA 并进行梯度稀释检测。结果表明,随着检测浓度的降低,检测阈值持续上升。当检测浓度低于结论值时,检测阈值就会降低:本文将 UES-LGG 定义为一种在临床实践中容易被误诊的肿瘤类型,因为它在手术中的阳性率极低。基于 qRT-PCR 的术中分子诊断技术的推广,大大减少了人工检测造成的误差,提高了手术中的疾病检出率。它为外科医生制定更精确的手术方案提供了理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Ultra-early stage lower-grade gliomas: How can we define and differentiate these easily misdiagnosed gliomas through intraoperative molecular diagnosis

Ultra-early stage lower-grade gliomas: How can we define and differentiate these easily misdiagnosed gliomas through intraoperative molecular diagnosis

Background

Some lower-grade gliomas (LGG) are difficult to distinguish morphologically from glial cell proliferation or inflammatory changes during surgery, leading to a high risk of incorrect diagnosis. It is crucial to differentiate between the two for making surgical decisions. We define these critical cases as “ultra early stage lower-grade gliomas (UES-LGG)”.

Methods

We analyzed 11 out of 13 cases diagnosed with “gliosis” or “inflammatory changes” during surgery who tested positive for isocitrate dehydrogenase (IDH). Additionally, we conducted qRT-PCR detection on 35 samples diagnosed with LGG during surgery and analyzed their DNA content within an effective circulating threshold range to infer the critical value between UES-LGG and LGG. We conducted experiments using five standardized samples to infer the limited range of accurate detection of UES-LGG during surgery.

Results

In the comparative analysis of 11 samples and 35 samples, it was found that while there was no significant difference in the average DNA detection concentration between the two groups (159.36 ± 83.3 ng/μL and 146.83 ± 122.43 ng/μL), there was a notable statistical variance in the detection threshold for positive mutations (31.78 ± 1.14 and 26.14 ± 2.69, respectively). This suggests that the IDH mutation rate may serve as an indicator for differentiation between the two groups. Subsequently, DNA was extracted from standardized IDH mutant samples and subjected to gradient dilution for detection purposes. The results indicated a consistent increase in detection threshold as detection concentration decreased. When the detection concentration fell below <0.1 ng/μL, it became impossible to carry out effective threshold range detections. To further identify the precise detection interval, we conducted gradient division once again and sought to simulate the functional relationship between DNA copy number and cycle threshold within this interval. The research revealed that when the minimum detection concentration exceeded 250 copies/μL, a 100% detection rate could be achieved.

Conclusions

This article defines UES-LGG as a tumor type easily misdiagnosed in clinical practice due to its extremely low positivity rate during surgery. The popularization of qRT-PCR based intraoperative molecular diagnosis greatly reduces errors caused by manual detection and improves disease detection rates during surgery. It provides a theoretical basis for more accurate surgical plans for surgeons.

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来源期刊
CNS Neuroscience & Therapeutics
CNS Neuroscience & Therapeutics 医学-神经科学
CiteScore
7.30
自引率
12.70%
发文量
240
审稿时长
2 months
期刊介绍: CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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