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唾液代谢组学鉴定犬口腔黑色素瘤和口腔鳞状细胞癌的生物标志物候选物。

Salivary metabolomic identification of biomarker candidates for oral melanoma and oral squamous cell carcinoma in dogs.

机构信息

Department of Clinical Sciences and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand.

The Metabolomics Innovation Centre, University of Alberta, Edmonton, Alberta, Canada.

出版信息

J Vet Intern Med. 2024 Jul-Aug;38(4):2293-2304. doi: 10.1111/jvim.17092. Epub 2024 May 4.

DOI:10.1111/jvim.17092
PMID:38703129
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11256132/
Abstract

BACKGROUND

Oral melanoma (OM) and oral squamous cell carcinoma (OSCC) are frequently diagnosed in dogs, presenting a challenge in distinguishing them from benign oral tumors (BN). Salivary metabolomic biomarkers offer a practical solution because of saliva's direct contact with tumors and the noninvasive nature of collection.

OBJECTIVE

Assess the diversity and abundance of the salivary metabolome in dogs with BN, OM, and OSCC using amine/phenol submetabolome analysis and high-performance chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS).

ANIMALS

Study included 11 BN, 24 OM, 10 OSCC, and 20 healthy control dogs.

METHODS

Case-control cross-sectional study was conducted to assess salivary submetabolic profiles in dogs with BN, OM, and OSCC and healthy dogs. Samples were labeled with C-dansyl chloride and analyzed using CIL LC-MS targeted to amine- and phenol-containing metabolites for amine/phenol submetabolome analysis.

RESULTS

Distinct clusters and significant differences in metabolite concentrations were observed among the oral cancer, BN, and control groups. A total of 154 and 66 metabolites showed significantly altered concentrations, particularly in OM and OSCC, respectively, when compared with BN (Padj < .05). Potential metabolic biomarkers were identified for each cancer, including decreased concentrations of seryl-arginine and sarcosine in OSCC. Moreover, high-confidence putative metabolites were identified, including an increase in tryptophyl-threonine and a decrease in 1,2-dihydroxynapthalene-6-sulfonic acid and hydroxyprolyl-hydroxyproline for OM.

CONCLUSIONS AND CLINICAL IMPORTANCE

We identified high coverage of the amine/phenol submetabolome, including seryl-arginine, and sarcosine, in OSCC. Our findings emphasize the potential of these biomarkers for distinguishing between oral OSCC and BN in dogs.

摘要

背景

口腔黑色素瘤(OM)和口腔鳞状细胞癌(OSCC)在狗中经常被诊断出来,这使得它们与良性口腔肿瘤(BN)区分具有挑战性。唾液代谢组生物标志物提供了一种实用的解决方案,因为唾液与肿瘤直接接触,并且采集是非侵入性的。

目的

使用胺/酚亚代谢组分析和高性能化学同位素标记液相色谱-质谱(CIL LC-MS)评估 BN、OM 和 OSCC 犬的唾液代谢组的多样性和丰度。

动物

研究包括 11 只 BN、24 只 OM、10 只 OSCC 和 20 只健康对照犬。

方法

进行病例对照横断面研究,以评估 BN、OM 和 OSCC 犬和健康犬的唾液亚代谢谱。使用 C-dansyl 氯化物标记样本,并使用针对含胺和酚代谢物的 CIL LC-MS 进行分析,用于胺/酚亚代谢组分析。

结果

在口腔癌、BN 和对照组之间观察到明显的聚类和代谢物浓度的显著差异。与 BN 相比,OM 和 OSCC 分别有 154 种和 66 种代谢物的浓度发生了显著变化(Padj <.05)。确定了每个癌症的潜在代谢生物标志物,包括 OSCC 中丝氨酸-精氨酸和肌氨酸的浓度降低。此外,还鉴定了高可信度的推定代谢物,包括 OM 中色氨酰-苏氨酸增加和 1,2-二羟基萘-6-磺酸和羟脯氨酸-羟脯氨酸减少。

结论和临床意义

我们确定了 OSCC 中胺/酚亚代谢组的高覆盖率,包括丝氨酸-精氨酸和肌氨酸。我们的发现强调了这些生物标志物在区分犬口腔 OSCC 和 BN 方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36a/11256132/7928d0862e64/JVIM-38-2293-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36a/11256132/400a8826f631/JVIM-38-2293-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36a/11256132/23d59caf3b4f/JVIM-38-2293-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36a/11256132/65439404c622/JVIM-38-2293-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36a/11256132/7928d0862e64/JVIM-38-2293-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36a/11256132/400a8826f631/JVIM-38-2293-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36a/11256132/23d59caf3b4f/JVIM-38-2293-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36a/11256132/65439404c622/JVIM-38-2293-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c36a/11256132/7928d0862e64/JVIM-38-2293-g002.jpg

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