Saliva in the diagnosis of diseases

Chen-Zi Zhang, Xing-Qun Cheng, Ji-Yao Li, Ping Zhang, Ping Yi, Xin Xu, Xue-Dong Zhou, Chen-Zi Zhang, Xing-Qun Cheng, Ji-Yao Li, Ping Zhang, Ping Yi, Xin Xu, Xue-Dong Zhou

Abstract

Saliva is secreted from the salivary glands and has multiple functions, including mouth cleaning and protection, antibacterial effects and digestion. With the rapid advancement in salivaomics, saliva is well recognized as a pool of biological markers. Saliva, as a non-invasive and safe source, could be a substitute for blood in the diagnosis and prognosis of diseases. This review summarizes the latest advancements in saliva-related studies and addresses the potential value of saliva in the early diagnosis of oral diseases, such as dental caries and periodontal disease, as well as cancer, diabetes and other systemic disorders. Saliva biomarkers range from changes in the biochemical indices of DNA, RNA and proteins to the diversification of microbiota structures. This study integrates data reported in the recent literature and discusses the clinical significance and prospects for the application of saliva in the early diagnosis of diseases, translational medicine and precision medicine.

References

    1. Wong DT. Salivaomics. J Am Dent Assoc 2012; 143 (10 Suppl): 19S–24S.
    1. Samaranayake L. Saliva as a diagnostic fluid. Int Dent J 2007; 57 (5): 295–299.
    1. Yang F, Zeng X, Ning K et al. Saliva microbiomes distinguish caries-active from healthy human populations. ISME J 2012; 6 (1): 1–10.
    1. Teng F, Yang F, Huang S et al. Prediction of early childhood caries via spatial-temporal variations of oral microbiota. Cell Host Microbe 2015; 18 (3): 296–306.
    1. O'Brien-Simpson NM, Burgess K, Brammar GC et al. Development and evaluation of a saliva-based chair-side diagnostic for the detection of Porphyromonas gingivalis. J Oral Microbiol 2015; 7: 29129.
    1. Hussain QA, McKay IJ, Gonzales-Marin C et al. Detection of adrenomedullin and nitric oxide in different forms of periodontal disease. J Periodontal Res 2016; 51 (1): 16–25.
    1. Poorsattar Bejeh-Mir A, Parsian H, Akbari Khoram M et al. Diagnostic role of salivary and GCF nitrite, nitrate and nitric oxide to distinguish healthy periodontium from gingivitis and periodontitis. Int J Mol Cell Med 2014; 3 (3): 138–145.
    1. Jenifer HD, Bhola S, Kalburgi V et al. The influence of cigarette smoking on blood and salivary super oxide dismutase enzyme levels among smokers and nonsmokers—a cross sectional study. J Tradit Complement Med 2015; 5 (2): 100–105.
    1. Ebersole JL, Nagarajan R, Akers D et al. Targeted salivary biomarkers for discrimination of periodontal health and disease(s). Front Cell Infect Microbiol 2015; 5: 62.
    1. Hendek MK, Erdemir EO, Kisa U. Evaluation of salivary procalcitonin levels in different periodontal diseases. J Periodontol 2015; 86 (6): 820–826.
    1. Rathod SR, Khan F, Kolte AP et al. Estimation of salivary and serum total sialic acid levels in periodontal health and disease. J Clin Diagn Res 2014; 8 (9): ZC19–ZC21.
    1. Banu S, Jabir NR, Mohan R et al. Correlation of Toll-like receptor 4, interleukin-18, transaminases, and uric acid in patients with chronic periodontitis and healthy adults. J Periodontol 2015; 86 (3): 431–439.
    1. Matthews D, McNeil K, McCulloch C et al. Adoption issues associated with a new periodontal screening tool: an online survey of Canadian dentists. J Can Dent Assoc 2013; 80: e57.
    1. Wang Y, Springer S, Mulvey CL et al. Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Sci Transl Med 2015; 7 (293): 293ra104.
    1. Triantos D, Horefti E, Paximadi E et al. Presence of human herpes virus-8 in saliva and non-lesional oral mucosa in HIV-infected and oncologic immunocompromised patients. Oral Microbiol Immunol 2004; 19 (3): 201–204.
    1. Park NJ, Zhou H, Elashoff D et al. Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res 2009; 15 (17): 5473–5477.
    1. Wong DT. Salivary diagnostics. Oper Dent 2012; 37 (6): 562–570.
    1. Vidotto A, Henrique T, Raposo LS et al. Salivary and serum proteomics in head and neck carcinomas: before and after surgery and radiotherapy. Cancer Biomark 2010; 8 (2): 95–107.
    1. Aziz S, Ahmed SS, Ali A et al. Salivary immunosuppressive cytokines IL-10 and IL-13 are significantly elevated in oral squamous cell carcinoma patients. Cancer Invest 2015; 33 (7): 318–328.
    1. Krishnan R, Thayalan DK, Padmanaban R et al. Association of serum and salivary tumor necrosis factor-α with histological grading in oral cancer and its role in differentiating premalignant and malignant oral disease. Asian Pac J Cancer Prev 2013; 15 (17): 7141–7148.
    1. Pushalkar S, Mane SP, Ji X et al. Microbial diversity in saliva of oral squamous cell carcinoma. FEMS Immunol Med Microbiol 2011; 61 (3): 269–277.
    1. Delaleu N, Mydel P, Kwee I et al. High fidelity between saliva proteomics and the biologic state of salivary glands defines biomarker signatures for primary Sjögren's syndrome. Arthritis Rheumatol 2015; 67 (4): 1084–1095.
    1. Khuder SA, Al-Hashimi I, Mutgi AB et al. Identification of potential genomic biomarkers for Sjögren's syndrome using data pooling of gene expression microarrays. Rheumatol Int 2015; 35 (5): 829–836.
    1. Hu S, Gao K, Pollard R et al. Preclinical validation of salivary biomarkers for primary Sjögren's syndrome. Arthritis Care Res 2010; 62 (11): 1633–1638.
    1. Aitken JP, Ortiz C, Morales-Bozo I et al. α-2-macroglobulin in saliva is associated with glycemic control in patients with type 2 diabetes mellitus. Dis Markers 2015; 2015: 128653.
    1. Abdolsamadi H, Goodarzi MT, Motemayel FA et al. Reduction of melatonin level in patients with type II diabetes and periodontal diseases. J Dent Res Dent Clin Dent Prospects 2014; 8 (3): 160–165.
    1. Barnes VM, Kennedy AD, Panagakos F et al. Global metabolomic analysis of human saliva and plasma from healthy and diabetic subjects, with and without periodontal disease. PLoS One 2014; 9 (8): e105181.
    1. Satish BN, Srikala P, Maharudrappa B et al. Saliva: a tool in assessing glucose levels in diabetes mellitus. J Int Oral Health 2014; 6 (2): 114–117.
    1. Kosaka T, Kokubo Y, Ono T et al. Salivary inflammatory cytokines may be novel markers of carotid atherosclerosis in a Japanese general population: the Suita study. Atherosclerosis 2014; 237 (1): 123–128.
    1. Miller C, Foley J, Floriano P et al. Utility of salivary biomarkers for demonstrating acute myocardial infarction. J Dent Res 2014; 93 (7 Suppl): 72S–79S.
    1. Zheng H, Li R, Zhang J et al. Salivary biomarkers indicate obstructive sleep apnea patients with cardiovascular diseases. Sci Rep 2014; 4: 7046.
    1. Parisi MR, Soldini L, Vidoni G et al. Point-of-care testing for HCV infection: recent advances and implications for alternative screening. New Microbiol 2014; 37 (4): 449–457.
    1. Korhonen EM, Huhtamo E, Virtala AM et al. Approach to non-invasive sampling in dengue diagnostics: exploring virus and NS1 antigen detection in saliva and urine of travelers with dengue. J Clin Virol 2014; 61 (3): 353–358.
    1. Nefzi F, Ben Salem NA, Khelif A et al. Quantitative analysis of human herpesvirus-6 and human cytomegalovirus in blood and saliva from patients with acute leukemia. J Med Virol 2015; 87 (3): 451–460.
    1. Sugimoto M, Wong DT, Hirayama A et al. Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles. Metabolomics 2010; 6 (1): 78–95.
    1. Zheng X, Chen F, Zhang J et al. Exosome analysis: a promising biomarker system with special attention to saliva. J Membr Biol 2014; 247 (11): 1129–1136.
    1. Kim VM, Ahuja N. Early detection of pancreatic cancer. Chin J Cancer Res 2015; 27 (4): 321–331.
    1. Humeau M, Vignolle-Vidoni A, Sicard F et al. Salivary microRNA in pancreatic cancer patients. PLoS One 2015; 10 (6): e0130996.
    1. Xie Z, Yin X, Gong B et al. Salivary microRNAs show potential as a noninvasive biomarker for detecting resectable pancreatic cancer. Cancer Prev Res (Phila) 2015; 8 (2): 165–173.
    1. Zhang L, Farrell JJ, Zhou H et al. Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer. Gastroenterology 2010; 138 (3): 949–957.
    1. Michaud DS, Izard J. Microbiota, oral microbiome, and pancreatic cancer. Cancer J 2014; 20 (3): 203–206.
    1. Farrell JJ, Zhang L, Zhou H et al. Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut 2012; 61 (4): 582–588.
    1. Arif S, Qudsia S, Urooj S et al. Blueprint of quartz crystal microbalance biosensor for early detection of breast cancer through salivary autoantibodies against ATP6AP1. Biosens Bioelectron 2015; 65: 62–70.
    1. Zhang L, Xiao H, Karlan S et al. Discovery and preclinical validation of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer. PLoS One 2010; 5 (12): e15573.
    1. Brooks MN, Wang J, Li Y et al. Salivary protein factors are elevated in breast cancer patients. Mol Med Rep 2008; 1 (3): 375–378.
    1. Agha-Hosseini F, Mirzaii-Dizgah I, Rahimi A. Correlation of serum and salivary CA15-3 levels in patients with breast cancer. Med Oral Patol Oral Cir Bucal 2009; 14 (10): e521–e524.
    1. Wei F, Lin CC, Joon A et al. Noninvasive saliva-based EGFR gene mutation detection in patients with lung cancer. Am J Respir Crit Care Med 2014; 190 (10): 1117–1126.
    1. Xiao H, Zhang L, Zhou H et al. Proteomic analysis of human saliva from lung cancer patients using two-dimensional difference gel electrophoresis and mass spectrometry. Mol Cell Proteomics 2012; 11 (2): M111.012112.
    1. Hizir MS, Balcioglu M, Rana M et al. Simultaneous detection of circulating oncomiRs from body fluids for prostate cancer staging using nanographene oxide. ACS Appl Mater Interfaces 2014; 6 (17): 14772–14778.
    1. Yang K, Li Y, Zhou X. [Overview of researches for Helicobacter pylori in oral cavity and stomach]. Huaxi Kouqiang Yixue Zazhi 2014; 32 (3): 314–318.
    1. Tripathi A, Tiwari B, Patil R et al. The role of salivary caffeine clearance in the diagnosis of chronic liver disease. J Oral Biol Craniofac Res 2015; 5 (1): 28–33.
    1. Pallos D, Leão MV, Togeiro FC et al. Salivary markers in patients with chronic renal failure. Arch Oral Biol 2015; 60 (12): 1784–1788.
    1. Chen D, Song N, Ni R et al. Saliva as a sampling source for the detection of leukemic fusion transcripts. J Transl Med 2014; 12: 321.
    1. Lau HC, Lee IK, Ko PW et al. Non-invasive screening for Alzheimer's disease by sensing salivary sugar using Drosophila cells expressing gustatory receptor (Gr5a) immobilized on an extended gate ion-sensitive field-effect transistor (EG-ISFET) biosensor. PLoS One 2015; 10 (2): e0117810.
    1. Cabras T, Sanna M, Manconi B et al. Proteomic investigation of whole saliva in Wilson's disease. J Proteomics 2015; 128: 154–163.
    1. Thijs JL, van Seggelen W, Bruijnzeel-Koomen C et al. New developments in biomarkers for atopic dermatitis. J Clin Med 2015; 4 (3): 479–487.

Source: PubMed

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