Identification of salivary metabolites for oral squamous cell carcinoma and oral epithelial dysplasia screening from persistent suspicious oral mucosal lesions
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To identify salivary metabolite biomarkers to differentiate patients with oral squamous cell carcinoma and oral epithelial dysplasia (OSCC/OED) from those with persistent suspicious oral mucosal lesions (PSOML).
Subjects and methods
Whole unstimulated saliva samples were collected from age-, sex-, and race-matched patients who had a lesion in the oral cavity and for whom open biopsies were performed. The patients included OSCC (n = 6), OED (n = 10), and PSOML (n = 32). Hydrophilic metabolites in saliva samples were comprehensively analyzed using capillary electrophoresis mass spectrometry. To evaluate the discrimination ability of a combination of multiple markers, a multiple logistic regression (MLR) model was developed to differentiate OSCC/OED from PSOML.
Six metabolites were significantly different in OSCC/OED compared with PSOML. From these six metabolites, ornithine, o-hydroxybenzoate, and ribose 5-phosphate (R5P) were used to develop the MLR model, which resulted in a high value for the area under receiver operating characteristic curve (AUC 0.871, 95% confidential interval (CI) 0.760–0.982; p < 0.001) to discriminate OSCC/OED from PSOML.
This is the first study to identify salivary metabolites that discriminate OSCC/OED from PSOML rather than from healthy controls. The profiles of salivary metabolites were significantly different between OSCC/OED and PSOML. The ability to discriminate OSCC/OED from PSOML is important for dentists who are not oral surgery specialists. These salivary metabolites showed potential for non-invasive screening to discriminate OSCC/OED from PSOML.
Salivary metabolites in this study showed potential for non-invasive screening to discriminate OSCC/OED from PSOML.
KeywordsMetabolites Oral squamous cell carcinoma Oral epithelial dysplasia Screening Saliva
We thank Edanz Group (www.edanzediting.com/ac), for editing a draft of this manuscript.
This work was supported by grants from Yamagata Prefecture, Tsuruoka, Japan, and the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) KAKENHI (16K11742 and 17K11897).
Compliance with ethical standards
Conflict of interest
David Wong is co-founder of RNAmeTRIX Inc., a molecular diagnostic company. He holds equity in RNAmeTRIX, and serves as a company Director and Scientific Advisor. The University of California also holds equity in RNAmeTRIX. Intellectual property that David Wong invented and which was patented by the University of California has been licensed to RNAmeTRIX. Dr. Wong is consultant to GlaxoSmithKlein, Wrigley, and Colgate-Palmolive. Masahiro Sugimoto is a co-founder of SalivaTech Co. LTD.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Ethics Committee of University of California, Los Angeles, Faculty (School) of Dentistry, approved this study protocol.
Informed consent was obtained from all individual participants included in the study.
- 8.Lind PO (1987) Malignant transformation in oral leukoplakia. Scand J Dent Res 95(6):449–455Google Scholar
- 10.Macey R, Walsh T, Brocklehurst P, Kerr AR, Liu JLY, Lingen MW, Ogden GR, Warnakulasuriya S, Scully C (2015) Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD010276.pub2
- 11.Rethman MP, Carpenter W, Cohen EE, Epstein J, Evans CA, Flaitz CM, Graham FJ, Hujoel PP, Kalmar JR, Koch WM, Lambert PM, Lingen MW, Oettmeier BW Jr, Patton LL, Perkins D, Reid BC, Sciubba JJ, Tomar SL, Wyatt AD Jr, Aravamudhan K, Frantsve-Hawley J, Cleveland JL, Meyer DM, American Dental C (2010) Association council on scientific affairs expert panel on screening for oral squamous cell, evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas. J Am Dent Assoc 141(5):509–520CrossRefGoogle Scholar
- 25.Takayama T, Tsutsui H, Shimizu I, Toyama T, Yoshimoto N, Endo Y, Inoue K, Todoroki K, Min JZ, Mizuno H, Toyo’Oka T (2016) Diagnostic approach to breast cancer patients based on target metabolomics in saliva by liquid chromatography with tandem mass spectrometry. Clin Chim Acta 452:18–26CrossRefGoogle Scholar
- 26.Levin VA, Uhm JH, Jaeckle KA, Choucair A, Flynn PJ, Yung WKA, Prados MD, Bruner JM, Chang SM, Kyritsis AP, Gleason MJ, Hess KR (2000) Phase III randomized study of postradiotherapy chemotherapy with alpha-difluoromethylornithine-procarbazine, N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosurea, vincristine (DFMO-PCV) versus PCV for glioblastoma multiforme. Clin Cancer Res 6(10):3878–3884Google Scholar
- 30.Sedaghat AR, Zhang Z, Begum S, Palermo R, Best S, Ulmer KM, Levine M, Zinreich E, Messing BP, Gold D, Wu AA, Niparko KJ, Kowalski J, Hirata RM, Saunders JR, Westra WH, Pai SI (2009) Prognostic significance of human papillomavirus in oropharyngeal squamous cell carcinomas. Laryngoscope 119(8):1542–1549CrossRefGoogle Scholar