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

Jau Song Yu, Yi Ting Chen, Wei Fan Chiang, Yung Chin Hsiao, Lichieh Julie Chu, Lai Chu Seei, Chi Sheng Wu, Hui Tzu Tu, Hsiao Wei Chen, Chia Chun Chen, Wei Chao Liao, Ya Ting Chang, Chih Ching Wu, Che Yi Lin, Shyun Yeu Liu, Shu Ti Chiou, Shu Li Chia, Kai Ping Chang, Chih Yen Chien, Su Wei ChangChee Jen Chang, John D. Young, Chia C. Pao, Yu Sun Chang, Leland H. Hartwell

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


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 inhouse 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.

Original languageEnglish (US)
Pages (from-to)11549-11554
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
StatePublished - Oct 11 2016


  • Biomarkers
  • Early detection
  • Oral cancer

ASJC Scopus subject areas

  • General


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