Saliva in the diagnosis of diseases

Abstract

Saliva has the potential to be used for diagnosis of a wide range of diseases. Xue-Dong Zhou and colleagues from China’s Sichuan University reviewed recent literature on the prospects of using saliva in the early diagnosis of diseases and in translational and precision medicine. They conclude that saliva can be used instead of blood to diagnose a variety of diseases. Saliva is simple and non-invasive to collect, and convenient to store. As well as containing high-quality DNA, it contains biomarkers that can be used to detect early stages of oral diseases, such as caries, gum disease, and oral cancer, in addition to pancreatic, breast, prostate and lung cancers and a variety of other conditions. Research in this area is still in its early stages and means of evaluating salivary content need to be standardized.

Keywords

diagnosis / oral diseases / precision medicine / saliva / systemic diseases

References

[1] Wong DT. Salivaomics. J Am Dent Assoc, 2012, 143(10 Suppl): 19S-24S.

[2] Samaranayake L. Saliva as a diagnostic fluid. Int Dent J, 2007, 57(5): 295-299.

[3] Yang F, Zeng X, Ning K. Saliva microbiomes distinguish caries-active from healthy human populations. ISME J, 2012, 6(1): 1-10.

[4] Teng F, Yang F, Huang S. Prediction of early childhood caries via spatial-temporal variations of oral microbiota. Cell Host Microbe, 2015, 18(3): 296-306.

[5] O'Brien-Simpson NM, Burgess K, Brammar GC. Development and evaluation of a saliva-based chair-side diagnostic for the detection of Porphyromonas gingivalis. J Oral Microbiol, 2015, 7: 29129.

[6] Hussain QA, McKay IJ, Gonzales-Marin C. Detection of adrenomedullin and nitric oxide in different forms of periodontal disease. J Periodontal Res, 2016, 51(1): 16-25.

[7] Poorsattar Bejeh-Mir A, Parsian H, Akbari Khoram M. 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.

[8] Jenifer HD, Bhola S, Kalburgi V. 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.

[9] Ebersole JL, Nagarajan R, Akers D. Targeted salivary biomarkers for discrimination of periodontal health and disease(s). Front Cell Infect Microbiol, 2015, 5: 62.

[10] Hendek MK, Erdemir EO, Kisa U. Evaluation of salivary procalcitonin levels in different periodontal diseases. J Periodontol, 2015, 86(6): 820-826.

[11] Rathod SR, Khan F, Kolte AP. Estimation of salivary and serum total sialic acid levels in periodontal health and disease. J Clin Diagn Res, 2014, 8(9): ZC19-ZC21.

[12] Banu S, Jabir NR, Mohan R. 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.

[13] Matthews D, McNeil K, McCulloch C. Adoption issues associated with a new periodontal screening tool: an online survey of Canadian dentists. J Can Dent Assoc, 2013, 80: e57.

[14] Wang Y, Springer S, Mulvey CL. 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.

[15] Triantos D, Horefti E, Paximadi E. 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.

[16] Park NJ, Zhou H, Elashoff D. Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res, 2009, 15(17): 5473-5477.

[17] Wong DT. Salivary diagnostics. Oper Dent, 2012, 37(6): 562-570.

[18] Vidotto A, Henrique T, Raposo LS. Salivary and serum proteomics in head and neck carcinomas: before and after surgery and radiotherapy. Cancer Biomark, 2010, 8(2): 95-107.

[19] Aziz S, Ahmed SS, Ali A. Salivary immunosuppressive cytokines IL-10 and IL-13 are significantly elevated in oral squamous cell carcinoma patients. Cancer Invest, 2015, 33(7): 318-328.

[20] Krishnan R, Thayalan DK, Padmanaban R. 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.

[21] Pushalkar S, Mane SP, Ji X. Microbial diversity in saliva of oral squamous cell carcinoma. FEMS Immunol Med Microbiol, 2011, 61(3): 269-277.

[22] Delaleu N, Mydel P, Kwee I. 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.

[23] Khuder SA, Al-Hashimi I, Mutgi AB. Identification of potential genomic biomarkers for Sjögren’s syndrome using data pooling of gene expression microarrays. Rheumatol Int, 2015, 35(5): 829-836.

[24] Hu S, Gao K, Pollard R. Preclinical validation of salivary biomarkers for primary Sjögren’s syndrome. Arthritis Care Res, 2010, 62(11): 1633-1638.

[25] Aitken JP, Ortiz C, Morales-Bozo I. α-2-macroglobulin in saliva is associated with glycemic control in patients with type 2 diabetes mellitus. Dis Markers, 2015, 2015: 128653.

[26] Abdolsamadi H, Goodarzi MT, Motemayel FA. 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.

[27] Barnes VM, Kennedy AD, Panagakos F. Global metabolomic analysis of human saliva and plasma from healthy and diabetic subjects, with and without periodontal disease. PLoS One, 2014, 9(8): e105181.

[28] Satish BN, Srikala P, Maharudrappa B. Saliva: a tool in assessing glucose levels in diabetes mellitus. J Int Oral Health, 2014, 6(2): 114-117.

[29] Kosaka T, Kokubo Y, Ono T. Salivary inflammatory cytokines may be novel markers of carotid atherosclerosis in a Japanese general population: the Suita study. Atherosclerosis, 2014, 237(1): 123-128.

[30] Miller C, Foley J, Floriano P. Utility of salivary biomarkers for demonstrating acute myocardial infarction. J Dent Res, 2014, 93(7 Suppl): 72S-79S.

[31] Zheng H, Li R, Zhang J. Salivary biomarkers indicate obstructive sleep apnea patients with cardiovascular diseases. Sci Rep, 2014, 4: 7046.

[32] Parisi MR, Soldini L, Vidoni G. Point-of-care testing for HCV infection: recent advances and implications for alternative screening. New Microbiol, 2014, 37(4): 449-457.

[33] Korhonen EM, Huhtamo E, Virtala AM. 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.

[34] Nefzi F, Ben Salem NA, Khelif A. 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.

[35] Sugimoto M, Wong DT, Hirayama A. Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles. Metabolomics, 2010, 6(1): 78-95.

[36] Zheng X, Chen F, Zhang J. Exosome analysis: a promising biomarker system with special attention to saliva. J Membr Biol, 2014, 247(11): 1129-1136.

[37] Kim VM, Ahuja N. Early detection of pancreatic cancer. Chin J Cancer Res, 2015, 27(4): 321-331.

[38] Humeau M, Vignolle-Vidoni A, Sicard F. Salivary microRNA in pancreatic cancer patients. PLoS One, 2015, 10(6): e0130996.

[39] Xie Z, Yin X, Gong B. Salivary microRNAs show potential as a noninvasive biomarker for detecting resectable pancreatic cancer. Cancer Prev Res (Phila), 2015, 8(2): 165-173.

[40] Zhang L, Farrell JJ, Zhou H. Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer. Gastroenterology, 2010, 138(3): 949-957.

[41] Michaud DS, Izard J. Microbiota, oral microbiome, and pancreatic cancer. Cancer J, 2014, 20(3): 203-206.

[42] Farrell JJ, Zhang L, Zhou H. Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut, 2012, 61(4): 582-588.

[43] Arif S, Qudsia S, Urooj S. Blueprint of quartz crystal microbalance biosensor for early detection of breast cancer through salivary autoantibodies against ATP6AP1. Biosens Bioelectron, 2015, 65: 62-70.

[44] Zhang L, Xiao H, Karlan S. Discovery and preclinical validation of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer. PLoS One, 2010, 5(12): e15573.

[45] Brooks MN, Wang J, Li Y. Salivary protein factors are elevated in breast cancer patients. Mol Med Rep, 2008, 1(3): 375-378.

[46] 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.

[47] Wei F, Lin CC, Joon A. Noninvasive saliva-based EGFR gene mutation detection in patients with lung cancer. Am J Respir Crit Care Med, 2014, 190(10): 1117-1126.

[48] Xiao H, Zhang L, Zhou H. 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.

[49] Hizir MS, Balcioglu M, Rana M. Simultaneous detection of circulating oncomiRs from body fluids for prostate cancer staging using nanographene oxide. ACS Appl Mater Interfaces, 2014, 6(17): 14772-14778.

[50] 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.

[51] Tripathi A, Tiwari B, Patil R. The role of salivary caffeine clearance in the diagnosis of chronic liver disease. J Oral Biol Craniofac Res, 2015, 5(1): 28-33.

[52] Pallos D, Leão MV, Togeiro FC. Salivary markers in patients with chronic renal failure. Arch Oral Biol, 2015, 60(12): 1784-1788.

[53] Chen D, Song N, Ni R. Saliva as a sampling source for the detection of leukemic fusion transcripts. J Transl Med, 2014, 12: 321.

[54] Lau HC, Lee IK, Ko PW. 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.

[55] Cabras T, Sanna M, Manconi B. Proteomic investigation of whole saliva in Wilson’s disease. J Proteomics, 2015, 128: 154-163.

[56] Thijs JL, van Seggelen W, Bruijnzeel-Koomen C. New developments in biomarkers for atopic dermatitis. J Clin Med, 2015, 4(3): 479-487.