Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan.
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.
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.
Jau-Song
JS
Yu
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.
Yi-Ting
YT
Chen
Department of Oral & Maxillofacial Surgery, Chi-Mei Medical Center, Liouying 736, Taiwan; School of Dentistry, National Yang Ming University, Taipei 112, Taiwan.
Wei-Fan
WF
Chiang
Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Liver Research Center, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
Yung-Chin
YC
Hsiao
Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Liver Research Center, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
Lichieh Julie
LJ
Chu
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.
Lai-Chu
LC
See
Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
Chi-Sheng
CS
Wu
Department of Public Health, Chang Gung University, Taoyuan 33302, Taiwan.
Hui-Tzu
HT
Tu
Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
Hsiao-Wei
HW
Chen
Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Department of Colorectal Surgery, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
Chia-Chun
CC
Chen
Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
Wei-Chao
WC
Liao
Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
Ya-Ting
YT
Chang
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.
Chih-Ching
CC
Wu
Department of Oral & Maxillofacial Surgery, Chi-Mei Medical Center, Liouying 736, Taiwan.
Che-Yi
CY
Lin
Department of Oral & Maxillofacial Surgery, Chi-Mei Medical Center, Liouying 736, Taiwan.
Shyun-Yeu
SY
Liu
Health Promotion Administration, Ministry of Health and Welfare, Taipei 115, Taiwan; Institute of Public Health, National Yang Ming University, Taipei 112, Taiwan.
Shu-Ti
ST
Chiou
Health Promotion Administration, Ministry of Health and Welfare, Taipei 115, Taiwan.
Shu-Li
SL
Chia
Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
Kai-Ping
KP
Chang
Department of Otolaryngology, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
Chih-Yen
CY
Chien
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.
Su-Wei
SW
Chang
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.
Chee-Jen
CJ
Chang
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.
John D
JD
Young
Department of Cell and Molecular Biology, Chang Gung University, Taoyuan 33302, Taiwan.
Chia C
CC
Pao
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.
Yu-Sun
YS
Chang
Center for Sustainable Health, Biodesign Institute, Arizona State University, Tempe, AZ 85281 ysc@mail.cgu.edu.tw lee.hartwell@asu.edu.
Leland H
LH
Hartwell
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002853:Chromatography, Liquid; D003710:Demography; D055088:Early Detection of Cancer; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D012307:Risk Factors; D012463:Saliva / Q000378:metabolism; D012471:Salivary Proteins and Peptides / Q000378:metabolism*; D013624:Taiwan
D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D012471:Salivary Proteins and Peptides
biomarkers; early detection; oral cancer
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