Deep sequencing salivary proteins for periodontitis using proteomics
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Saliva is a bodily fluid transuded from gingival crevice fluid and blood and contains many proteins. Proteins in saliva have been studied as markers for periodontal diseases. Mass spectrometric analysis is applied to investigate biomarker proteins that are related to periodontitis.
Material and methods
Saliva samples were collected from 207 participants including 36 pairs matched for age, sex, and smoking who joined Yangpyeong health cohort. Periodontitis was defined by 2005 5th European guideline. Shotgun proteomics was applied to detect proteins from saliva samples. Principal component analysis and Ingenuity Pathway Analysis for canonical pathway and protein pathway were applied. Protein-protein interaction was also applied. Enzyme-linked immunosorbent assay (ELISA) was used to verify the candidate protein markers among another matched participants (n = 80).
Shotgun proteomics indicated that salivary S100A8 and S100A9 were candidate biomarkers for periodontitis. ELISA confirmed that both salivary S100A8 and S100A9 were higher in those with periodontitis compared to those without periodontitis (paired-t test, p < 0.05).
Our proteomics data showed that S100A8 and S100A9 in saliva could be candidate biomarkers for periodontitis. The rapid-test-kit using salivary S100A8 and S100A9 will be a practical tool for reducing the risk of periodontitis and promotion of periodontal health.
A rapid-test-kit using salivary biomarkers, S100A8 and S100A9, could be utilized by clinicians and individuals for screening periodontitis, which might reduce the morbidity of periodontitis and promote periodontal health.
KeywordsProteomics Saliva Periodontitis Protein biomarker Ingenuity Pathway Analysis
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (NRF-2017M3A9B6062984).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This cross-sectional study was approved by institutional review board (SNU SOD N0: S-D20170045).
Informed consent was obtained from all individual participants included in the study.
- 3.Wu Y, Shu R, Luo LJ, Ge LH, Xie YF (2009) Initial comparison of proteomic profiles of whole unstimulated saliva obtained from generalized aggressive periodontitis patients and healthy control subjects. J Periodontal Res 44(5):636–644. https://doi.org/10.1111/j.1600-0765.2008.01172.x CrossRefPubMedGoogle Scholar
- 5.Mertens B, Orti V, Vialaret J, Gibert P, Relaño-Ginés A, Lehmann S, de Périère DD, Hirtz C (2018) Assessing a multiplex-targeted proteomics approach for the clinical diagnosis of periodontitis using saliva samples. Bioanalysis 10(1):35–45. https://doi.org/10.4155/bio-2017-0218 CrossRefPubMedGoogle Scholar
- 6.Orti V, Mertens B, Vialaret J, Gibert P, Relaño-Ginés A, Lehmann S, Deville de Périère D, Hirtz C (2018) Data from a targeted proteomics approach to discover biomarkers in saliva for the clinical diagnosis of periodontitis. Data Brief 18:294–299. https://doi.org/10.1016/j.dib.2018.03.036 CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Ahn YB, Shin MS, Han DH, Sukhbaatar M, Kim MS, Shin HS, Kim HD (2016) Periodontitis is associated with the risk of subclinical atherosclerosis and peripheral arterial disease in Korean adults. Atherosclerosis 251:311–318. https://doi.org/10.1016/j.atherosclerosis.2016.07.898 CrossRefPubMedGoogle Scholar
- 16.Good DM, Thongboonkerd V, Novak J, Bascands JL, Schanstra JP, Coon JJ, Dominiczak A, Mischak H (2007) Body fluid proteomics for biomarker discovery: lessons from the past hold the key to success in the future. J Proteome Res 6(12):4549–4555. https://doi.org/10.1021/pr070529w CrossRefPubMedGoogle Scholar
- 23.Streckfus CF, Mayorga-Wark O, Arreola D, Edwards C, Bigler L, Dubinsky WP (2008) Breast cancer related proteins are present in saliva and are modulated secondary to ductal carcinoma in situ of the breast. Cancer Investig 26(2):159–167. https://doi.org/10.1080/07357900701783883 CrossRefGoogle Scholar
- 25.Bandhakavi S, Stone MD, Onsongo G, van Riper SK, Griffin TJ (2009) A dynamic range compression and three-dimensional peptide fractionation analysis platform expands proteome coverage and the diagnostic potential of whole saliva. J Proteome Res 8(12):5590–5600. https://doi.org/10.1021/pr900675w CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Zia A, Khan S, Bey A, Gupta ND, Mukhtar-Un-Nisar S (2011) Oral biomarkers in the diagnosis and progression of periodontal diseases. Biol Med 3:45–52Google Scholar
- 29.Tonetti MS, Claffey N, European Workshop in Periodontology group C (2005) Advances in the progression of periodontitis and proposal of definitions of a periodontitis case and disease progression for use in risk factor research - Group C Consensus report of the 5th European workshop in periodontology. J Clin Periodontol 32:210–213. https://doi.org/10.1111/j.1600-051X.2005.00822.x CrossRefPubMedGoogle Scholar
- 32.Tsuchida S, Satoh M, Umemura H, Sogawa K, Kawashima Y, Kado S, Sawai S, Nishimura M, Kodera Y, Matsushita K, Nomura F (2012) Proteomic analysis of gingival crevicular fluid for discovery of novel periodontal disease markers. Proteomics 12(13):2190–2202. https://doi.org/10.1002/pmic.201100655 CrossRefPubMedGoogle Scholar
- 35.Kojima T, Andersen E, Sanchez JC, Wilkins MR, Hochstrasser DF, Pralong WF, Cimasoni G (2000) Human gingival crevicular fluid contains MRP8 (S100A8) and MRP14 (S100A9), two calcium-binding proteins of the S100 family. J Dent Res 79(2):740–747. https://doi.org/10.1177/00220345000790020701 CrossRefPubMedGoogle Scholar
- 38.Burt BS, Research, Science and Therapy Committee of the American Academy of Periodontology (2005) Therapy Committee of the American Academy of, position paper: epidemiology of periodontal diseases. J Periodontol 76(8):1406–1419. https://doi.org/10.1902/jop.2005.76.8.1406 CrossRefPubMedGoogle Scholar
- 39.Baliban RC, Sakellari D, Li Z, DiMaggio PA, Garcia BA, Floudas CA (2012) Novel protein identification methods for biomarker discovery via a proteomic analysis of periodontally healthy and diseased gingival crevicular fluid samples. J Clin Periodontol 39(3):203–212. https://doi.org/10.1111/j.1600-051X.2011.01805.x CrossRefPubMedGoogle Scholar
- 41.Ramseier CA, Kinney JS, Herr AE, Braun T, Sugai JV, Shelburne CA, Rayburn LA, Tran HM, Singh AK, Giannobile WV (2009) Identification of pathogen and host-response markers correlated with periodontal disease. J Periodontol 80(3):436–446. https://doi.org/10.1902/jop.2009.080480 CrossRefPubMedPubMedCentralGoogle Scholar