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皮秒红外激光质谱法鉴定出用于 10 秒诊断特定皮肤癌类型的代谢物谱:概念验证可行性研究。

Picosecond Infrared Laser Mass Spectrometry Identifies a Metabolite Array for 10 s Diagnosis of Select Skin Cancer Types: A Proof-of-Concept Feasibility Study.

机构信息

Techna Institute for the Advancement of Technology for Health, University Health Network, 100 College Street, Toronto, Ontario M5G 1P5, Canada.

Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada.

出版信息

Anal Chem. 2022 Dec 6;94(48):16821-16830. doi: 10.1021/acs.analchem.2c03918. Epub 2022 Nov 17.

Abstract

Currently, a large number of skin biopsies are taken for each true skin cancer case detected, creating a need for a rapid, high sensitivity, and specificity skin cancer detection tool to reduce the number of unnecessary biopsies taken from benign tissue. Picosecond infrared laser mass spectrometry (PIRL-MS) using a hand-held sampling probe is reported to detect and classify melanoma, squamous cell carcinoma, and normal skin with average sensitivity and specificity values of 86-95% and 91-98%, respectively (at a 95% confidence level) solely requiring 10 s or less of total data collection and analysis time. Classifications are not adversely affected by specimen's quantity of melanin pigments and are mediated by a number of metabolic lipids, further identified herein as potential biomarkers for skin cancer-type differentiation, 19 of which were sufficient here (as a fully characterized metabolite array) to provide high specificity and sensitivity classification of skin cancer types. detection was demonstrated in an intradermal melanoma mouse model wherein sampling did not cause significant discomfort. PIRL-MS sampling is further shown to be compatible with downstream gross histopathologic evaluations despite loss of tissue from the immediate laser sampling site(s) and can be configured using selective laser pulses to avoid thermal damage to normal skin. Therefore, PIRL-MS may be employed as a decision-support tool to reduce both the subjectivity of clinical diagnosis and the number of unnecessary biopsies currently required for skin cancer screening.

摘要

目前,对于每一个检测到的真实皮肤癌病例,都需要进行大量的皮肤活检,这就需要一种快速、高灵敏度和特异性的皮肤癌检测工具,以减少从良性组织中进行不必要的活检数量。据报道,使用手持式采样探头的皮秒红外激光质谱(PIRL-MS)可以检测和分类黑素瘤、鳞状细胞癌和正常皮肤,平均灵敏度和特异性值分别为 86-95%和 91-98%(置信水平为 95%),仅需 10 秒或更短的总数据采集和分析时间。分类不受标本中黑色素含量的影响,而是由多种代谢脂质介导,这里进一步确定了其中 19 种代谢脂质作为皮肤癌类型分化的潜在生物标志物,这些代谢脂质足以(作为完全表征的代谢物阵列)提供皮肤癌类型的高特异性和灵敏度分类。在真皮黑色素瘤小鼠模型中证明了这种方法的有效性,其中采样不会引起明显的不适。尽管从直接激光采样部位(多个)损失了组织,但 PIRL-MS 采样与下游大体组织病理学评估仍然兼容,并且可以使用选择性激光脉冲进行配置,以避免对正常皮肤造成热损伤。因此,PIRL-MS 可作为一种决策支持工具,以减少皮肤癌筛查中目前所需的临床诊断的主观性和不必要活检的数量。

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