Systematic verification of saliva-based biosignatures for oral cancer via targeted metabolomics

Authors

• Ya-Ju Hsieh, Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan
• Yu Chang, Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan
• Chi Yang, Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan
• Nai Hsuan Teng, Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan
• Jau-Song Yu, Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan
• Kai-Ping Chang, Department of Otolaryngology-Head & Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
• Wen-Chen Chen, Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan
• Lichieh Julie Chu, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
• Yi-Ting Chen, Kidney Research Center, Department of Nephrology, LinKou Chang Gung Memorial Hospital, Taoyuan, TaiwanFollow

Keywords

Biomarkers, MRM-MS, OPMD, Oral cancer, Targeted metabolomics

Abstract

Oral squamous cell carcinoma (OSCC) remains a major global health challenge, and early detection is essential for improving patient outcomes. To identify reliable salivary biomarkers, we performed a targeted metabolomics study using ¹³C₂/¹²C₂-dansylation, integrating candidate metabolites from published OSCC metabolomics datasets and systematically verifying them through LC-MRM-MS. A panel of 26 metabolites was quantified in saliva samples from 299 subjects, including healthy controls (n = 98), oral potentially malignant disorders (OPMD I, n = 50; OPMD II, n = 53), and OSCC patients (n = 98). Among these, cadaverine, N-acetylcadaverine, choline, glycine, and tryptophan were significantly dysregulated across disease groups. Cadaverine, N-acetylcadaverine and choline were consistently elevated in OSCC and showed progressive increases with disease stages, whereas glycine levels declined. A four-metabolite panel (cadaverine, N-acetylcadaverine, choline, glycine) demonstrated strong diagnostic performance in distinguishing OSCC from healthy controls (AUC = 0.91). Correlation analyses further revealed coordinated regulation among polyamine-related metabolites, suggesting a reprogramming of ornithine–polyamine metabolism in OSCC progression. In conclusion, we establish a verified salivary metabolite panel with high discriminatory power for OSCC detection. These findings highlight polyamine-associated metabolic alterations as a hallmark of malignant transformation in the oral cavity and support salivary metabolomics as a clinically accessible tool for non-invasive screening and risk stratification.

Abstract Image

Recommended Citation

Hsieh, Ya-Ju; Chang, Yu; Yang, Chi; Teng, Nai Hsuan; Yu, Jau-Song; Chang, Kai-Ping; Chen, Wen-Chen; Chu, Lichieh Julie; and Chen, Yi-Ting (2026) "Systematic verification of saliva-based biosignatures for oral cancer via targeted metabolomics," Journal of Food and Drug Analysis: Vol. 34 : Iss. 1 , Article 9.
Available at: https://doi.org/10.38212/2224-6614.3586

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