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犬类嗅觉可区分体内侵袭性黑色素瘤、基底细胞癌、良性痣和健康皮肤:挥发性有机化合物排放差异的原理初步研究。

Invasive melanoma in vivo can be distinguished from basal cell carcinoma, benign naevi and healthy skin by canine olfaction: a proof-of-principle study of differential volatile organic compound emission.

机构信息

Department of Dermatology, Amersham Hospital, Buckinghamshire Healthcare NHS Trust, Amersham, HP7 0JD, U.K.

Search Dogs UK, 9 Church Road, Thornton-Cleveleys, Lancashire, FY5 2TX, U.K.

出版信息

Br J Dermatol. 2016 Nov;175(5):1020-1029. doi: 10.1111/bjd.14887. Epub 2016 Sep 11.

DOI:10.1111/bjd.14887
PMID:27454583
Abstract

BACKGROUND

Volatile organic compounds (VOCs) are continuously released by the body during normal metabolic processes, but their profiles change in the presence of cancer. Robust evidence that invasive melanoma in vivo emits a characteristic VOC signature is lacking.

OBJECTIVES

To conduct a canine olfactory, proof-of-principle study to investigate whether VOCs from invasive melanoma are distinguishable from those of basal cell carcinoma (BCC), benign naevi and healthy skin in vivo.

METHODS

After a 13-month training period, the dog's ability to discriminate melanoma was evaluated in 20 double-blind tests, each requiring selection of one melanoma sample from nine controls (three each of BCC, naevi and healthy skin; all samples new to the dog).

RESULTS

The dog correctly selected the melanoma sample on nine (45%) occasions (95% confidence interval 0·23-0·68) vs. 10% expected by chance alone. A one-sided exact binomial test gave a P-value of < 0·01, supporting the hypothesis that samples were not chosen at random but that some degree of VOC signal from the melanoma samples significantly increased the probability of their detection. Use of a discrete-choice model confirmed melanoma as the most influential of the recorded medical/personal covariates in determining the dog's choice of sample. Accuracy rates based on familiar samples during training were not a reliable indicator of the dog's ability to distinguish melanoma, when confronted with new, unknown samples.

CONCLUSIONS

Invasive melanoma in vivo releases odorous VOCs distinct from those of BCC, benign naevi and healthy skin, adding to the evidence that the volatile metabolome of melanoma contains diagnostically useful biomarkers.

摘要

背景

挥发性有机化合物(VOCs)在正常代谢过程中会不断从体内释放,但在癌症存在的情况下其谱发生变化。目前缺乏有力的证据表明体内侵袭性黑色素瘤会发出特征性的 VOC 特征。

目的

进行犬类嗅觉的初步研究,以调查体内侵袭性黑色素瘤的 VOC 是否可与基底细胞癌(BCC)、良性痣和健康皮肤的 VOC 区分开来。

方法

在 13 个月的训练期后,评估狗区分黑色素瘤的能力,共进行 20 次双盲测试,每次测试要求从 9 个对照(BCC、痣和健康皮肤各 3 个;所有样本均为狗未接触过的新样本)中选择一个黑色素瘤样本。

结果

狗在 9 次(45%)正确选择了黑色素瘤样本(95%置信区间 0.23-0.68),而单独凭机会选择的次数为 10%。单侧精确二项式检验的 P 值<0.01,支持这样的假设,即样本不是随机选择的,而是黑色素瘤样本的某种程度的 VOC 信号显著增加了其被检测到的概率。使用离散选择模型证实了黑色素瘤是记录的医学/个人协变量中对狗选择样本影响最大的因素。在训练过程中基于熟悉样本的准确率并不是狗区分黑色素瘤能力的可靠指标,当面对新的未知样本时更是如此。

结论

体内侵袭性黑色素瘤释放的挥发性有机化合物与 BCC、良性痣和健康皮肤不同,这进一步证明了黑色素瘤挥发性代谢组包含有诊断价值的生物标志物。

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