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

Sekkarin Ploypetch; Xian Luo; Shuang Zhao; Sittiruk Roytrakul; Liang Li; Gunnaporn Suriyaphol

doi:10.1111/jvim.17092

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

J Vet Intern Med. 2024 May 4. doi: 10.1111/jvim.17092. Online ahead of print.

Authors

Sekkarin Ploypetch¹, Xian Luo², Shuang Zhao², Sittiruk Roytrakul³, Liang Li^{2

4}, Gunnaporn Suriyaphol^{5

6}

Affiliations

¹ Department of Clinical Sciences and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand.
² The Metabolomics Innovation Centre, University of Alberta, Edmonton, Alberta, Canada.
³ Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.
⁴ Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
⁵ Biochemistry Unit, Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.
⁶ Center of Excellence for Companion Animal Cancer, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.

PMID: 38703129
DOI: 10.1111/jvim.17092

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 ¹²C-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.

Keywords: canine oral melanoma; canine oral squamous cell carcinoma; metabolomic biomarkers; saliva.

Abstract

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