Purpose: This study aims to explore the presence of informative protein biomarkers in the human saliva proteome and to evaluate their potential for detection of oral squamous cell carcinoma (OSCC).
Experimental Design: Whole saliva samples were collected from patients (n = 64) with OSCC and matched healthy subjects (n = 64). The proteins in pooled whole saliva samples of patients with OSCC (n = 16) and matched healthy subjects (n = 16) were profiled using shotgun proteomics based on C4 reversed-phase liquid chromatography for prefractionation, capillary reversed-phase liquid chromatography with quadruple time-of-flight mass spectrometry, and Mascot sequence database searching. Immunoassays were used for validation of the candidate biomarkers on a new group of OSCC (n = 48) and matched healthy subjects (n = 48). Receiver operating characteristic analysis was exploited to evaluate the diagnostic value of discovered candidate biomarkers for OSCC.
Results: Subtractive proteomics revealed several salivary proteins at differential levels between the OSCC patients and matched control subjects. Five candidate biomarkers were successfully validated using immunoassays on an independent set of OSCC patients and matched healthy subjects. The combination of these candidate biomarkers yielded a receiver operating characteristic value of 93%, sensitivity of 90%, and specificity of 83% in detecting OSCC.
Conclusion: Patient-based saliva proteomics is a promising approach to searching for OSCC biomarkers . The discovery of these new targets may lead to a simple clinical tool for the noninvasive diagnosis of oral cancer . Long-term longitudinal studies with large populations of individuals with oral cancer and those who are at high risk of developing oral cancer are needed to validate these potential biomarkers.
Shen Hu1, Martha Arellano1, Pinmanee Boontheung2, Jianghua Wang1, Hui Zhou1, Jiang Jiang1, David Elashoff7, Roger Wei1, Joseph A. Loo2,3,4 and David T. Wong1,3,5,6
Authors' Affiliations: 1 Oral Biology and Medicine Division and Dental Research Institute, School of Dentistry, 2 Department of Chemistry and Biochemistry, 3 Jonsson Comprehensive Cancer Center, 4 Department of Biological Chemistry, David Geffen School of Medicine, 5 Division of Head and Neck Surgery/Otolaryngology, School of Medicine, 6 Henry Samueli School of Engineering and Applied Science, and 7 Department of Biostatistics, School of Public Health, University of California at Los Angeles, Los Angeles, California
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