title: Identification of salivary metabolomic biomarkers for oral cancer screening.
abstract: The objective of this study was to explore salivary metabolite biomarkers by profiling both saliva and tumor tissue samples for oral cancer screening. Paired tumor and control tissues were obtained from oral cancer patients and whole unstimulated saliva samples were collected from patients and healthy controls. The comprehensive metabolomic analysis for profiling hydrophilic metabolites was conducted using capillary electrophoresis time-of-flight mass spectrometry. In total, 85 and 45 metabolites showed significant differences between tumor and matched control samples, and between salivary samples from oral cancer and controls, respectively (P < 0.05 correlated by false discovery rate); 17 metabolites showed consistent differences in both saliva and tissue-based comparisons. Of these, a combination of only two biomarkers yielded a high area under receiver operating characteristic curves (0.827; 95% confidence interval, 0.726-0.928, P < 0.0001) for discriminating oral cancers from controls. Various validation tests confirmed its high generalization ability. The demonstrated approach, integrating both saliva and tumor tissue metabolomics, helps eliminate pseudo-molecules that are coincidentally different between oral cancers and controls. These combined salivary metabolites could be the basis of a clinically feasible method of non-invasive oral cancer screening.
authors.affiliation: Department of Dentistry, Oral and Maxillofacial Plastic and Reconstructive Surgery, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.|Department of Oral Science, Division of Orthodontics, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Kanagawa 238-8580, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Department of Dentistry, Oral and Maxillofacial Plastic and Reconstructive Surgery, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kitabatake
authors.affiliation: Department of Dentistry, Oral and Maxillofacial Plastic and Reconstructive Surgery, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Sugano
authors.affiliation: Department of Dentistry, Oral and Maxillofacial Plastic and Reconstructive Surgery, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan.
authors.forename: Marina
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.
authors.forename: Miku
authors.initials: M
authors.lastname: Kaneko
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.
authors.forename: Sana
authors.initials: S
authors.lastname: Ota
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Hiwatari
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.
authors.forename: Ayame
authors.initials: A
authors.lastname: Enomoto
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Tomita
authors.affiliation: Department of Dentistry, Oral and Maxillofacial Plastic and Reconstructive Surgery, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Iino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor