1. Introduction

Saliva is an encouraging medium to be used in the early detection, diagnosis and monitoring of oral and systemic diseases, specifically for the purpose of personalized medicine by incorporating point-of care technology platforms in the clinical settings. Though, saliva collection is easy, fast, cheap, safe, does not require specialized equipment and can be performed at home [1]. The normal daily production of saliva varies between 0.5 and 1.5 l. Saliva is an acidic biofluid, derived from the three major salivary glands (parotid, submandibular, sublingual) as well as from minor glands (labial, buccal, lingual, and palatal tissues). It is composed in vast majority of water (99%), while other constituents occur in trace amounts, including proteins and both inorganic (sodium, potassium, calcium, magnesium, chloride, etc.) and organic

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

constituents (amylases, peroxidase, lipase, mucins, lysozyme, lactoferrins, cystatins, hormones, etc.) [2]. Salivary composition is very diverse (RNA, DNA, proteins, metabolites, and microbiota), and may be utilized for diagnostic purposes. Most importantly, salivary components may vary in their concentrations and levels depending on the individual's health or disease status. Thus, real-time monitoring of salivary data can provide useful translational clinical applications in the detection of various human oral and systemic diseases. The development of the recent technologies based on salivary diagnostics will help to introduce screening programs to enable early detection and monitoring of the disease [3].

The currently accepted gold standard methods for proteomic analyses include: triple depletion of high abundance proteins (removal of albumins, alpha amylase and immunoglobulins), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE), two-dimensional gel electrophoresis (2-DE), mass spectrometry (label free qMS), ELISA (enzyme-linked immunosorbent assay) and Western blotting [2, 6]. Other advanced methods include electrospray ionization (ESI), matrix-assisted laser desorption ionization (MALDI), quadrupole/linear ion trap, time-offlight (TOF), quadrupole TOF (QTOP), Fourier transform ion cyclotron resonance (FT-ICR), or

Salivary Diagnostics

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http://dx.doi.org/10.5772/intechopen.73372

Recently, a great focus has been put on identification of salivary protein biomarkers for various human oral and systemic diseases such as: pancreatic cancer, Sjogren's syndrome, oral cancer, lung cancer, orthodontically induced root resorption, etc. [2, 5]. The proteomics delivers an alternative ideal and non-invasive diagnostic tool, more sensitive, and safer for detecting the disease status. In addition, the depletion of high abundance proteins from saliva contributes to significant increase in the detectability of less abundant salivary proteins [5, 8]. There are known three major methods of high-abundance protein removal [9]: enzyme-substrate absorption method used for alpha-amylase affinity removal [8], immunodepletion method and com-

Proteomic analysis of saliva is commonly used in the diagnostics of oral diseases as well as general health disorders such as oral candidiasis [11], oral squamous cell carcinoma (OSCC) [12], glossodynia [13], head and neck squamous cell cancer [14], Sjögren's syndrome [15], HIV [11], autism [16], fibromyalgia [17], breast cancer [18], lung cancer, melanoma [19] or pancre-

Various mediators associated with oral cancer are released from cells due to malignant conditions and have been analyzed in saliva samples, like cytokines, chemokines, interferon-gamma (IFN-γ), interleukins (IL-1β, IL-6 and -8, Il-4 and -10), tumor necrosis factors (TNF-α), transforming growth factor-beta-1 (TGF-β1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and endothelin [20]. In case of oral squamous cell carcinoma, elevated levels of NF- κB-dependent cytokines have been observed in saliva [21]. Other potential protein biomarkers include IL-6 and S100A9 [22] or BGH3, MMP9 and PDIA3 [23]. In addition, increased salivary expression levels of MMP1 and MMP3 in OSCC patients can indicate more advanced stage of disease [12], while adenosine deaminase might be indicative

Transcriptomics (gene expression profiling) is the quantitative study of an organism's transcriptome, all RNA transcripts present in a cell. The information is recorded in the genome and expressed through transcription. These data can be used for capturing marked changes in expression levels of specific genes in the detection of various human diseases [2, 25]. Transcriptomics encompasses a great diversity of RNA species including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), and small RNAs such as microRNAs (miRNAs), transfer RNAs (tRNAs), piwi-interacting RNA (piRNA), etc. The mRNAs play an important

the OrbiTrap, MS/MS, MALDI-MS or targeted HPLC-ESI-MS/MS [7].

binatorial peptide ligand library (CPLL) [10].

of early stage of oral tongue cancer [24].

atic cancer [7].

2.2. Transcriptomics

Saliva is an important biofluid with lots of various biological functions including lubrication, chewing, swallowing, sensation, digestion and protection of oral mucosa against biological, mechanical, and chemical factors as well as infections [2].
