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一种用于通过皮秒红外激光质谱法在10秒内诊断常见脊柱肿瘤类型的分子阵列。

A molecular array for 10-second diagnosis of common spinal tumor types with picosecond infrared laser mass spectrometry.

作者信息

Fiorante Alexa, Woolman Michael, Munoz David G, Kiyota Taira, Ye Lan Anna, Farahmand Yasmine, Vlaminck Darah, Talbot Francis O, Das Sunit, Kellett Sorcha, Giuffrida Christine, Zadeh Gelareh, Ginsberg Howard J, Aman Ahmed, Zarrine-Afsar Arash

机构信息

Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.

Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

出版信息

Neuro Oncol. 2025 Sep 17;27(8):2060-2072. doi: 10.1093/neuonc/noaf047.

Abstract

BACKGROUND

Improving the surgical outcomes for commonly occurring spinal neoplasms of extradural and intradural extramedullary origins requires precise intraoperative diagnosis provided by highly trained neuropathologists.

METHODS

Through a retrospective study of n = 319 patient specimens, verified where appropriate by learning curve analysis to be sufficient for statistically significant observations, we aimed to assess the utility of 10-second picosecond infrared laser mass spectrometry (MS; PIRL-MS) for non-subjective diagnosis of major spinal tumor types of metastatic carcinoma, schwannoma, and meningiomas.

RESULTS

The sensitivity and specificity values of spinal tumor-type diagnosis (based on n = 182 independent specimens) were (93% ± 1)% and (97% ± 2)%, respectively. This classification utilizes n = 41 cellular lipids including phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, and ceramides whose identities were established using high-resolution tandem MS. Furthermore, the accuracy of diagnosis of a model that contained n = 97 meningioma and n = 106 schwannoma was not drastically influenced by the presence of n = 54 additional intradural extramedullary spinal neoplasms of myxopapillary ependymoma, neurofibroma, paraganglioma, and solitary fibrous tumor types in the differential diagnosis, confirming the generalizability and robustness of the identified molecular array in rendering correct classification even in the presence of data not seen previously by the model.

CONCLUSIONS

The identified lipids form a "molecular array" for robust diagnosis of meningioma and schwannoma tumors by non-pathologists in a manner similar to genomic, transcriptomic, or methylomic arrays used to diagnose brain cancer types, albeit on a much faster timescale of seconds as opposed to hours.

摘要

背景

改善硬膜外和硬膜内髓外常见脊柱肿瘤的手术效果需要训练有素的神经病理学家提供精确的术中诊断。

方法

通过对n = 319例患者标本进行回顾性研究,并在适当情况下通过学习曲线分析验证其足以进行具有统计学意义的观察,我们旨在评估10秒皮秒红外激光质谱(MS;PIRL-MS)对转移性癌、神经鞘瘤和脑膜瘤等主要脊柱肿瘤类型进行非主观诊断的效用。

结果

脊柱肿瘤类型诊断的敏感性和特异性值(基于n = 182个独立标本)分别为(93% ± 1)%和(97% ± 2)%。该分类利用了n = 41种细胞脂质,包括磷脂酰胆碱、鞘磷脂、磷脂酰乙醇胺和神经酰胺,其身份通过高分辨率串联质谱确定。此外,包含n = 97例脑膜瘤和n = 106例神经鞘瘤的模型的诊断准确性,在鉴别诊断中不受另外n = 54例黏液乳头型室管膜瘤、神经纤维瘤、副神经节瘤和孤立性纤维瘤类型的硬膜内髓外脊柱肿瘤的影响,这证实了所确定的分子阵列即使在存在模型之前未见过的数据的情况下,在进行正确分类方面的通用性和稳健性。

结论

所确定的脂质形成了一种“分子阵列”,非病理学家可以通过它以类似于用于诊断脑癌类型的基因组、转录组或甲基化组阵列的方式,对脑膜瘤和神经鞘瘤进行稳健诊断,尽管时间尺度要快得多,以秒为单位而非小时。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c5/12448866/ee02a73bdea4/noaf047_fig1.jpg

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