Evidence map›Paper›PMID 27663741›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

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 See, Chi-Sheng Wu, Hui-Tzu Tu, Hsiao-Wei Chen, Chia-Chun Chen and 15 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
9.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Biomedicines · 2026
    Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Biological biomarkers of oral cancer.Periodontology 2000 · 2024
    Review
  14. Article
  15. Article
  16. Review
  17. Evaluation of salivary tumor necrosis factorFrontiers in oral health · 2024
    Article
  18. Review
  19. Article
  20. Review

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 8 institutions in 2 countries.

Jau-Song YuDepartment 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.
Yi-Ting ChenMolecular 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.
Wei-Fan ChiangDepartment of Oral & Maxillofacial Surgery, Chi-Mei Medical Center, Liouying 736, Taiwan; School of Dentistry, National Yang Ming University, Taipei 112, Taiwan.
Yung-Chin HsiaoMolecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Liver Research Center, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
Lichieh Julie ChuMolecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Liver Research Center, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
Lai-Chu SeeBiostatistics 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.
Chi-Sheng WuMolecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
Hui-Tzu TuDepartment of Public Health, Chang Gung University, Taoyuan 33302, Taiwan.
Hsiao-Wei ChenMolecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
Chia-Chun ChenMolecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan; Department of Colorectal Surgery, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
Wei-Chao LiaoMolecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
Ya-Ting ChangMolecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
Chih-Ching WuMolecular 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.
Che-Yi LinDepartment of Oral & Maxillofacial Surgery, Chi-Mei Medical Center, Liouying 736, Taiwan.
Shyun-Yeu LiuDepartment of Oral & Maxillofacial Surgery, Chi-Mei Medical Center, Liouying 736, Taiwan.
Shu-Ti ChiouHealth Promotion Administration, Ministry of Health and Welfare, Taipei 115, Taiwan; Institute of Public Health, National Yang Ming University, Taipei 112, Taiwan.
Shu-Li ChiaHealth Promotion Administration, Ministry of Health and Welfare, Taipei 115, Taiwan.
Kai-Ping ChangDepartment of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou 33375, Taiwan.
Chih-Yen ChienDepartment of Otolaryngology, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
Su-Wei ChangClinical 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.
Chee-Jen ChangClinical 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.
John D YoungCenter 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.
Chia C PaoDepartment of Cell and Molecular Biology, Chang Gung University, Taoyuan 33302, Taiwan.
Yu-Sun ChangMolecular 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.
Leland H HartwellCenter for Sustainable Health, Biodesign Institute, Arizona State University, Tempe, AZ 85281 ysc@mail.cgu.edu.tw lee.hartwell@asu.edu.
Chang Gung Memorial Hospital · TWChang Gung University · TWChi Mei Medical Center · TWMinistry of Health and Welfare · TWArizona State University · USKaohsiung Chang Gung Memorial Hospital · TWMing Chi University of Technology · TWNational Yang Ming Chiao Tung University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Biomarkers, TumorCarcinoma, Squamous CellChromatography, LiquidDemographyEarly Detection of CancerEndoplasmic Reticulum Chaperone BiPFemaleFollow-Up StudiesHumansMaleMass SpectrometryMiddle AgedMouth NeoplasmsNeoplasm StagingRisk FactorsSalivaBiomarkers, TumorEndoplasmic Reticulum Chaperone BiPHSPA5 protein, humanSalivary Proteins and Peptidesbiomarkersearly detectionoral cancer

Identifiers

PMID27663741
PMCPMC5068314
OpenAlexW2521198002

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.