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Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):11549-11554. Epub 2016 Sep 23.

Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan.

Author information

1
Department of Cell and Molecular Biology, Chang Gung University, Taoyuan 33302, Taiwan; Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Liver Research Center, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
2
Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Department of Biomedical Sciences, Chang Gung University, Taoyuan 33302, Taiwan; Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan 33302, Taiwan; Department of Nephrology, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
3
Department of Oral & Maxillofacial Surgery, Chi-Mei Medical Center, Liouying 736, Taiwan; School of Dentistry, National Yang Ming University, Taipei 112, Taiwan.
4
Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Liver Research Center, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
5
Biostatistics Consulting Center, Chang Gung University, Taoyuan 33302, Taiwan; Department of Public Health, Chang Gung University, Taoyuan 33302, Taiwan; Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
6
Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
7
Department of Public Health, Chang Gung University, Taoyuan 33302, Taiwan.
8
Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Department of Colorectal Surgery, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
9
Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan 33302, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
10
Department of Oral & Maxillofacial Surgery, Chi-Mei Medical Center, Liouying 736, Taiwan.
11
Health Promotion Administration, Ministry of Health and Welfare, Taipei 115, Taiwan; Institute of Public Health, National Yang Ming University, Taipei 112, Taiwan.
12
Health Promotion Administration, Ministry of Health and Welfare, Taipei 115, Taiwan.
13
Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
14
Department of Otolaryngology, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
15
Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
16
Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Department of Cardiology, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
17
Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 33302, Taiwan; Biochemical Engineering Research Center, Ming Chi University of Technology, New Taipei City 243, Taiwan; Chang Gung Biotechnology, Taipei 105, Taiwan; Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10065.
18
Department of Cell and Molecular Biology, Chang Gung University, Taoyuan 33302, Taiwan.
19
Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou 33375, Taiwan; ysc@mail.cgu.edu.tw lee.hartwell@asu.edu.
20
Center for Sustainable Health, Biodesign Institute, Arizona State University, Tempe, AZ 85281 ysc@mail.cgu.edu.tw lee.hartwell@asu.edu.

Abstract

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.

KEYWORDS:

biomarkers; early detection; oral cancer

PMID:
27663741
PMCID:
PMC5068314
DOI:
10.1073/pnas.1612368113
[Indexed for MEDLINE]
Free PMC Article

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