Saliva Proteome Research Articles

Proteomics of saliva, plasma, and salivary gland tissue in Sjögren's syndrome and non-Sjögren patients identify novel biomarker candidates

ObjectiveThe aim of this study was to characterize and compare the proteome in whole saliva, plasma, and salivary gland tissue in patients with primary Sjögren's syndrome (pSS) and patients having symptoms of pSS, but not fulfilling the classification criteria, and to search for diagnostic biomarker candidates for pSS. MethodsLiquid chromatography tandem mass spectrometry was conducted on whole saliva, plasma, and labial salivary gland tissue samples from 24 patients with pSS and 16 non-Sjögren control subjects (non-pSS). Gene Ontology (GO)-terms and Kyoto Encyclopedia of Genes and Genomes (KEGG)-pathways were applied for functional annotation. Results1013 proteins were identified in whole saliva, 219 in plasma, and 3166 in salivary gland tissue. In saliva, 40 proteins differed significantly between the two groups. In pSS, proteins involved in immunoinflammatory processes were upregulated, whereas proteins related to salivary secretion were downregulated. The combination of neutrophil elastase, calreticulin, and tripartite motif-containing protein 29 yielded a receiver-operating characteristic (ROC) value of 0.97 (CI 0.93–1.00). Protein expression in plasma and salivary gland tissue did not differ between the patient groups. ConclusionThe salivary proteome of patients with pSS differed from that of non-pSS patients, indicating that saliva proteomics represents a promising non-invasive diagnostic tool for pSS. SignificancePrimary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease, which clinically may present with a wide variety of symptoms and signs. Symptoms of dry eyes and dry mouth due to lacrimal and salivary gland dysfunction are prominent, but not pathognomonic, and an extensive diagnostic work-up including blood tests and labial salivary gland biopsy is often required to distinguish pSS from non-pSS. In this study, we used high throughput proteomics and identified a non-invasive biomarker candidate comprising a combination of three different upregulated salivary proteins, which enables differentiation between patients with pSS and non-pSS patients with an accuracy of 97%. In the future, this could contribute to earlier, more accurate and less costly diagnosis of pSS.

Changes in the Salivary Proteome Associated With Canine Pyometra.

The present study evaluated for the first time changes in the saliva proteome in bitches with pyometra through a high-throughput quantitative proteomic analysis. The aims were to explore whether saliva composition could reflect the physiopathological changes occurring in canine pyometra and to identify potential biomarkers of the disease. Saliva samples from six healthy (H) and six bitches with pyometra (P) were analyzed using tandem mass tags–based approach. Additionally, 15 samples were used for the validation of changes in haptoglobin (Hp) concentration in saliva of dogs with pyometra. Proteomic analysis quantified 707 proteins in saliva. Comparison of the two groups revealed 16 unique proteins significantly modulated in saliva, with S100A calcium-binding protein 12 (S100A12), vimentin, and Hp the most up-regulated in canine pyometra. According to PANTHER (Protein Analysis Through Evolutionary Relationships) classification tool, these proteins are mainly related to proinflammatory mediators, acute-phase proteins, and sepsis. In conclusion, it can be stated that there are changes in various proteins in saliva in canine pyometra reflecting different physiopathological changes occurring in this disease. These proteins could be a source of potential non-invasive biomarkers for this disease that should be confirmed in future studies.

Use of Saliva for Diagnosis and Monitoring the SARS-CoV-2: A General Perspective.

In this report, updated information and future perspectives about the use of saliva as a sample for laboratory analysis of the Covid-19 are highlighted. Saliva can be used for the direct detection of the SARS-CoV-2 virus, the quantification of the specific immunoglobulins produced against it, and for the evaluation of the non-specific, innate immune response of the patient. Moreover, a deeper knowledge of potential changes in the saliva proteome in this disease may allow the identification of new diagnostic and prognostic biomarkers, or even help our understanding of the mechanisms associated with the disease. With the development of appropriate sample collection and processing methods and the use of adequate assays, saliva can provide useful clinical information about the disease and could be potentially included in guidelines for sample collection for the diagnosis, disease management, and control of Covid-19.

Salivary proteome signatures in the early and middle stages of human pregnancy with term birth outcome

The establishment and maintenance of pregnancy in humans proceed through a continuous change of biochemical and biophysical processes. It requires a constant interaction between the fetus and the maternal system. The present prospective study aims to elucidate changes in salivary proteome from the early to middle stages of term pregnancy, and establishing an expressional trajectory for modulated proteins. To date, a comprehensive characterization of the longitudinal salivary proteome in pregnancy has not been performed and it is our immediate interest. In the discovery phase, maternal saliva (N = 20) at 6–13, 18–21, and 26–29 weeks of gestation was analyzed using level-free proteomics (SWATH-MS) approach. The expression levels of 65 proteins were found to change significantly with gestational age and distributed into two distinct clusters with a unique expression trajectory. The results revealed that altered proteins are involved in maternal immune modulation, metabolism, and host defense mechanism. Further, verification of 12 proteins was employed using targeted mass spectrometry (MRM-MS) in a separate subset of saliva (N = 14). The MRM results of 12 selected proteins confirmed a similar expression pattern as in SWATH-MS analysis. Overall, the results not only demonstrate the longitudinal maternal saliva proteome for the first time but also set the groundwork for comparative analysis between term birth and adverse pregnancy outcomes.

Saliva proteomics from children with caries at different severity stages.

To perform a comparative analysis of saliva protein profile of patients with early childhood caries at different levels of severity and caries-free individuals. Stimulated saliva samples were collected from 126 children (2-6years old), classified according to the ICDAS II, and divided into 3 groups (n=42): caries-free (CF), enamel caries (EC), and dentine caries (DC). Samples were digested and analyzed by nanoUPLC coupled with a mass spectrometry. Data analyses were conducted with Progenesis QI for Proteomics Software v2.0. Gene Ontology (GO) terms and protein-protein interaction analysis were obtained. A total of 306 proteins (≈6 peptides) were identified. Among them, 122 were differentially expressed in comparisons among children with different caries status. Out of the 122 proteins, the proteins E2AK4 and SH3L2 were exclusively present in groups CF and EC, respectively, and 8 proteins (HAUS4, CAH1, IL36A, IL36G, AIMP1, KLHL8, KLH13, and SAA1) were considered caries-related proteins when compared to caries-free children; they were up-regulated proteins in the caries groups (EC and DC). The identification of exclusive proteins for caries-free or carious-related conditions may help in understanding the mechanisms of caries and predicting risk as well as advancing in caries control or anti-caries approaches.

Changes in Serum and Salivary Proteins in Canine Mammary Tumors.

Simple SummaryThe present study describes for the first time the differences in the serum and saliva proteomes between healthy bitches and bitches with mammary tumors using a high-throughput proteomic approach. More than 1000 proteins were identified and 35 in serum and 49 in saliva were significantly modulated. Additionally, their related pathways were discussed in order to improve understanding of the pathophysiology of the disease and one protein, serum albumin, was further validated. The results of the present study could be a source of potential biomarkers for canine mammary tumors in saliva and serum and increase the knowledge on the pathophysiology of the disease.The aim of this study was to evaluate changes in serum and saliva proteomes in canine mammary tumors (CMT) using a high-throughput quantitative proteomic analysis in order to potentially discover possible biomarkers of this disease. Proteomes of paired serum and saliva samples from healthy controls (HC group, n = 5) and bitches with CMT (CMT group, n = 5) were analysed using a Tandem Mass Tags-based approach. Twenty-five dogs were used to validate serum albumin as a candidate biomarker in an independent sample set. The proteomic analysis quantified 379 and 730 proteins in serum and saliva, respectively. Of those, 35 proteins in serum and 49 in saliva were differentially represented. The verification of albumin in serum was in concordance with the proteomic data, showing lower levels in CMT when compared to the HC group. Some of the modulated proteins found in the present study such as haptoglobin or S100A4 have been related to CMT or human breast cancer previously, while others such as kallikrein-1 and immunoglobulin gamma-heavy chains A and D are described here for the first time. Our results indicate that saliva and serum proteomes can reflect physiopathological changes that occur in CMT in dogs and can be a potential source of biomarkers of the disease.

Changes in Salivary Proteome in Response to Bread Odour.

It is widely recognized that smelling food results in a mouth-watering feeling and influences appetite. However, besides changes in volume, little is known about the effects that food odours have on the composition of saliva. The aim of the present study was to access the effects that smelling bread has on saliva proteome and to compare such effects with those of chewing and ingesting it. Besides a significant increase in saliva flow rate, together with a decrease in total protein concentration, bread odour induced changes in the proportion of different salivary proteins. The expression levels of two spots of cystatins and two spots of amylase increased due to olfactory stimulation, similar to what happened with bread mastication, suggesting that odour can allow anticipation of the type of food eaten and consequently the physiological oral changes necessary to that ingestion. An interesting finding was that bread odour increased the expression levels of several protein spots of immunoglobulin chains, which were decreased by both bread or rice mastication. This may be of clinical relevance since food olfactory stimulation of salivary immunoglobulins can be used to potentiate the oral immune function of saliva. Moreover, the effects of bread odour in the levels of salivary proteins, previously observed to be involved in oral food processing led to the hypothesis of an influence of this odour in the sensory perception of foods further ingested. Further studies are needed to elucidate this point, as well as whether the changes observed for bread odour are specific, or if different food odours lead to similar salivary proteome responses.

Time-resolved proteomic profile of Amblyomma americanum tick saliva during feeding.

Amblyomma americanum ticks transmit more than a third of human tick-borne disease (TBD) agents in the United States. Tick saliva proteins are critical to success of ticks as vectors of TBD agents, and thus might serve as targets in tick antigen-based vaccines to prevent TBD infections. We describe a systems biology approach to identify, by LC-MS/MS, saliva proteins (tick = 1182, rabbit = 335) that A. americanum ticks likely inject into the host every 24 h during the first 8 days of feeding, and towards the end of feeding. Searching against entries in GenBank grouped tick and rabbit proteins into 27 and 25 functional categories. Aside from housekeeping-like proteins, majority of tick saliva proteins belong to the tick-specific (no homology to non-tick organisms: 32%), protease inhibitors (13%), proteases (8%), glycine-rich proteins (6%) and lipocalins (4%) categories. Global secretion dynamics analysis suggests that majority (74%) of proteins in this study are associated with regulating initial tick feeding functions and transmission of pathogens as they are secreted within 24–48 h of tick attachment. Comparative analysis of the A. americanum tick saliva proteome to five other tick saliva proteomes identified 284 conserved tick saliva proteins: we speculate that these regulate critical tick feeding functions and might serve as tick vaccine antigens. We discuss our findings in the context of understanding A. americanum tick feeding physiology as a means through which we can find effective targets for a vaccine against tick feeding.

Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva

Salivary proteins facilitate food perception and digestion, maintain the integrity of the mineralized tooth and oral epithelial surfaces, and shield the oro-digestive tract from environmental hazards and invading pathogens. Saliva, as one of the easiest to collect body fluids, also serves in diagnostic applications, with its proteins providing a window to body health. However, despite the availability of the human saliva proteome, the origins of individual proteins remain unclear. To bridge this gap, we analyzed the transcriptomes of 27 tissue samples derived from the three major types of human adult and fetal salivary glands and integrated these data with the saliva proteome and the proteomes and transcriptomes of 28+ other human organs, with tissue expression confirmed by 3D microscopy. Using these tools, we have linked saliva proteins to their source for the first time, an outcome with significant implications for basic research and diagnostic applications. Furthermore, our study represents the first comparative transcriptomic analysis of human adult and fetal exocrine organs, providing evidence that functional specialization occurs late in salivary gland development, and is driven mainly by the transcription of genes encoding secreted saliva proteins. Moreover, we found that dosage of abundant saliva proteins secreted by the salivary glands is primarily regulated at the transcriptional level, and that secreted proteins can be synthesized by distinct subsets of serous acinar cells, revealing hitherto unrecognized heterogeneity in the acinar cell lineage. Our results reveal the functional underpinnings of these secretory organs, paving the way for future investigations into saliva biology and pathology.

Upregulation of tropomyosin alpha-4 chain in patients\u2019 saliva with oral squamous cell carcinoma as demonstrated by Phage display

Patients with oral squamous cell carcinoma (OSCC) present significant alterations in their saliva proteome. We have used the shotgun Phage Display (PD) technology to identify candidate proteins that were upregulated in saliva of OSCC by selecting ligands to salivary proteins from a single-chain variable fragment (scFv) PD combinatorial library. After two selection cycles, the highly reactive clone scFv-D09 was able to distinguish saliva of OSCC patients from healthy subjects by enzyme-linked immunosorbent assay (ELISA) with sensitivity and specificity of 96.67%. Additionally, the scFv-D09 clone presented a positive immunostaining for invasive malignant epithelial cells in the connective tissue, keratin pearls in the OSCC, and ducts of salivary glands. We have further identified the target protein as the tropomyosin alpha-4 chain (TPM4) by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry, and its binding to the scFV-D09 was demonstrated by bioinformatics. Briefly, we have identified TPM4 as upregulated salivary protein in patients with OSCC, which plays a central role in stabilizing cytoskeleton actin filaments, probably linked with tumor tissue remodeling. Long-term longitudinal studies are needed to validate TPM4 as a potential marker of a malignant process.

Salivary Proteomic Analysis of Betel Nut (Areca catechu) Consumers by Mass Spectrometry Revealed Primary Indication of Oral Malignancies

Areca nut is the fourth most widely used addictive and psychoactive substance consumed by approximately 10% of the world’s population. The use of areca nut is estimated to account for up to 50% of oral cancer in the low-income, and middle-income countries. In the present study, the effect of betel nut chewing on saliva proteomics was investigated by using mass spectrometry. Matrix-assisted laser desorption ionization mass spectrometry was used to generate a profile of the peptides in betel nut consumers and control group. We found 13 peptide peaks which were significantly altered (p < 0.05) in the betel nut addicts when compared with the control group. These significant peptides signals were corresponding to protein cystatin SN (CST1), cystatin S (CST4), alpha 2 macroglobulin (A2M), complement C3 (C3), apolipoprotein E (APOE), serum albumin (ALB), matrix metalloproteinase-9 (MMP-9), deleted in malignant brain tumor protein 1 (DMBT1), zinc-alpha-2-glycoprotein (ZAG), and protein S100A8. The correlation analysis of significant peptides intensities with the history of betel nut chewing was also performed. The peptides of CST1 and CST4 showed negative correlation, whereas the peptides of the MMP-9, DMBT1, APOE, and C3 showed positive correlation with significant differences. STRING analysis of these proteins revealed that most of these proteins are interacting with each other. The present study identifies a number of proteins in a significantly different abundance in the betel nut consumers group. Some of these proteins are the reported biomarkers of several oral malignancies, which implies that the usage of betel nut could lead to inflammation, and development of oral cancer.

Phenotyping multiple subsets in Sj\xf6gren\u2019s syndrome: a salivary proteomic SWATH-MS approach towards precision medicine

BackgroundThis proof of concept study was aimed at characterizing novel salivary biomarkers specific for different subsets in primary Sjögren’s syndrome (pSS) in order to improve patients’ profiling.MethodspSS patients were stratified in three subgroups according to both (a) focus score in the minor salivary gland biopsies (i.e. intensity of immune cell infiltration in the tissue) and (b) unstimulated salivary flow rate. Healthy volunteers were included as controls. A nano-HPLC-SWATH-MS approach was used for the analysis of saliva proteome of different subsets.ResultsWe found 203 differentially expressed proteins in pSS patients with respect to controls with evident differences in the expression of normal constituents of the human salivary proteome (i.e. prolactin-inducible protein, proline-rich proteins, cystatins) and several mediators of inflammatory processes. The comparative analysis of the pSS phenotypes unrevealed 63 proteins that were shared and specifically modulated in the three subsets of pSS patients converging on several inflammatory pathways. Among them S100A protein appeared of particular interest merging on IL-12 signaling and being significantly influenced by either salivary flow impairment or intensity of immune cell infiltration in the tissue.ConclusionsConstellations of proteins, including S100A proteins, characterize different pSS subsets reflecting either salivary gland dysfunction or inflammation. Salivary proteomics may foster future research projects ultimately aimed at developing personalized treatments for pSS patients.

Identification of possible new salivary biomarkers of stress in sheep using a high-resolution quantitative proteomic technique

The aim of this study was to identify biological pathways and proteins differentially expressed in the saliva proteome of sheep after the application of a model of stress, using high-resolution quantitative proteomics. In addition, one of the proteins differently expressed was verified and evaluated as a possible biomarker of stress in this species. Saliva paired samples from eight sheep before and after the application of a model of stress based on shearing were analysed using tandem mass tags (TMT). The TMT analysis allowed for the identification of new stress-related metabolic pathways and revealed 13 proteins, never described in saliva of sheep, that were differentially expressed between before and after the stress. Six of these proteins pertain to four major metabolic pathways affected, namely: canonical glycolysis, oxygen transport, neural nucleus development, and regulation of actin cytoskeleton reorganization. The rest of proteins were unmapped original proteins such as acyl-coenzyme-A-binding protein; complement C3; alpha-2-macroglobulin isoform-X1; type-II small proline-rich protein; lactoferrin; secretoglobin family-1D-member; and keratin, type-II cytoskeletal 6. Of these proteins, based on its biological significance and specific immunoassay availability, lactoferrin was selected for further validation. The immunoassay intra- and inter-assay coefficients of variation were lower than 13%. The method showed good linearity under dilution and recovery, and the detection limit was low enough to detect salivary lactoferrin levels. A significant decrease (P < 0.01) in salivary lactoferrin concentration in the sheep following the application of the model of stress was observed, suggesting that this protein could be a potential salivary biomarker of stress situations in sheep.

Comparative proteomic analysis of saliva from dogs with and without obesity-related metabolic dysfuntion

Dogs develop only some of the components of the human metabolic syndrome (MetS). Thus, in order to study possible MetS-related alterations in dogs, human MetS criteria were adapted to define canine MetS or so-called obesity-related metabolic dysfunction (ORMD). The main objective of this study was to identify changes in the salivary proteome of obese dogs with ORMD in comparison with obese dogs without ORMD which may constitute potential salivary biomarkers for assessing ORMD. In a first phase, 12 adult obese dogs with ORMD (N = 6) and without ORMD (N = 6) were included in the study. Subsequently, and with the aim of validating and strengthening the results, additional 12 obese dogs (6 with and 6 without ORMD) were tested in an independent experiment following the same protocol. Saliva samples were subjected to a quantitative proteomics analysis and the levels of nine salivary proteins were found to be significantly different between groups, among them those which had greatest fold-change were proteins involved in glycolysis and oxidative stress. In conclusion, despite metabolic syndrome to include different combinations of diseases, the observation of differences in salivary proteome suggests a potential of this fluid to understand the pathophysiology of the disease. SignificanceThis is the first study evaluating proteomes of saliva in dogs, as a non invasive sample, in order to increase knowledge about the metabolic/physiopathological changes related to obesity-related metabolic dysfunction (ORMD) together with the identification of potential biomarkers for its diagnosis. As approximately 20% of dogs with naturally occurring obesity were described to suffer ORMD associated with insulin resistance and hypoadiponectinemia, the fact that indicate possible links between ORMD and associated diseases.

Sample Treatment for Saliva Proteomics.

The preanalytical phase of saliva proteomics/peptidomics, which includes sample collection, handling, and storage, represents a major challenge for any researcher that envisions sensitive and high-throughput analyses, coupled to well-controlled study design. The methodology used to collect saliva determines the contribution of each salivary gland to saliva composition with impact on data retrieved from proteomics/peptidomics. The awareness of the importance of this step in the analysis of saliva has prompted the proposal of several collection strategies. Moreover, numerous commercial devices are available in an attempt to routine the procedures. However, whatever the chosen method, procedures should be kept simple, standardized to get better reproducibility and repeatability on saliva proteomics analysis. Sample preservation is also a key step in saliva proteomics/peptidomics, and the implemented lab procedures should avoid posttranslational modifications such as proteolysis, as well as protein precipitation.In this chapter, we provide recommendations for saliva sampling and preservation, envisaging to standardize procedures that facilitate the use of saliva in clinical applications and the translation of proteomics data to diagnosis and/or definition of therapeutic targets.

Liquid Chromatography Mass Spectrometry (LC-MS) analysis in determining the saliva protein of orthodontic patients during retention phase

BackgroundThe biological responses involved during retention phase have been studied for many years but little is known about the effect of saliva proteome during retention phase of post-orthodontic treatment. This study aims to identify the protein profiles during retention phase in relation to biological processes involved by Liquid Chromatography Mass Spectrometry (LC-MS) approach.Material and MethodsA total of 5 ml of unstimulated saliva was collected from each subject (10 non-orthodontic patients and 15 post-orthodontic patients with 6-months retention phase). Samples were then subjected to LC-MS analysis. The expressed proteins were identified and compared between groups. Incisor irregularity for both maxilla and mandible were determined with Little’s Irregularity Index at 6-months retention phase.Results146 proteins and 135 proteins were expressed in control and 6-months retention phase group respectively. 15 proteins were identified to be co-expressed between groups. Immune system process was only detected in 6-months retention phase group. Detected protein in immune system process was identified as Tyrosine-protein kinase Tec. Statistical significant of incisor irregularity was only found in mandible at 6-months retention phase.ConclusionsOur study suggests that immune system process protein which is Tyrosine-protein kinase Tec could be used as biomarker for prediction of stability during retention phase of post-orthodontic treatment. Key words:Orthodontics, proteomics, retention, LC-MS, saliva.

Diagnostic potential of saliva proteome analysis: a review and guide to clinical practice.

Proteomic techniques have become popular in medicine and dentistry because of their widespread use in analyzing bodily fluids such as blood, saliva, urine, and gingival crevicular fluids as well as hard tissues such as enamel, dentine, and cementum. This review is a guide to proteomic techniques in general dentistry, summarizing techniques and their clinical application in understanding and diagnosing diseases and their use in identifying biomarkers of various diseases.

Saliva-Omics in Plasma Cell Disorders — Proof of Concept and Potential As a Non-Invasive Tool for Monitoring Disease Burden and MRD Status

Salivaomics has exciting potential for the diagnosis and monitoring of malignancy, evidence of which has been reported in oral cancer (Sahibzada et al., 2017), head and neck malignancies (Citrin et al., 2012) and ovarian cancer (Chen et al., 1990). It has been observed that approximately 40% of cancer, stroke and cardiovascular disease biomarkers are present in whole saliva (Loo et al., 2010). Salivaomics has become an area of great interest in disease diagnosis over the last number of years, following the footsteps of the other “omics” based diagnostic tools. Saliva has been referred to as “the mirror of the body” as it gives an insight into the internal pathological state (Lee and Wong, 2009). As saliva is considered a fast, inexpensive and non-invasive method of sample collection, the future of diagnosis, early detection, monitoring and prediction of progression of disease has been thought to lie here.Monoclonal gammopathy of undetermined significance (MGUS) is characterised as a premalignant precursor tumours of MM. It has been seen that the majority of MM cases develop from MGUS (Weiss et al., 2009), leading to the need for biomarkers to monitor disease progression and explore the mechanism of malignant transformation.Serum and saliva samples were collected from 18 newly diagnosed MM patients and 8 MGUS patients, peptides were purified using the filter aided sample preparation (FASP) method and samples were prepared for label-free liquid chromatography mass spectrometry (LC-MS/MS) using an LTQ Orbitrap XL mass spectrometrer (Thermo Fisher Scientific). Proteins were analysed using the MaxQuant and Perseus software for mass-spectrometry (MS)-based proteomics data analysis, UniProtKB-Swiss Prot database and KEGG Pathway database.The abundance of proteins in saliva from MGUS compared to newly diagnosed MM was analysed using label-free mass spectrometry. A panel of 6 significant proteins was identified. Fatty Acid Binding Protein 5 (FABP5) was detected in elevated levels in saliva from MM patients compared to MGUS. The increased expression was verified using western blotting. Fatty Acid Binding Protein 5 (FABP5) is known to promote cell proliferation, survival and migration (Wang et al., 2006). FABP5 has been observed to aid in the proliferation of cancer and has been seen to be overexpressed in multiple cancer types such as breast (Levi et al., 2013), prostate (Morgan et al., 2008) and HCC (Ohata et al., 2017). FABP5 has seen to link closely with poor outcome and unfavourable clinical parameters in MM (Waheed et al., 2013).Additionally, analysis was performed on serial MM patient saliva samples during treatment. A panel of significant proteins was identified when comparing the saliva proteome during treatment the abundance of many of the detected proteins mirrored response to treatment (Table 1). For example, Transglutaminase 3 (TGM3) was observed as being decreased in abundance in saliva from patients in remission. TGM3 is expressed in brain, small intestine, mucosa and skin and has been shown to be required for the cross-linking of the structural protein trichohyalin and the keratin intermediate filaments to form a rigid structure within the inner root sheath cells (Hitomi, 2005). Overexpression of TGM3 has been observed to induce oesophageal cancer (EC) cell invasion, migration and proliferation. It has also been noted that TGM3 promotes apoptosis in EC in vitro (Li et al., 2016). TGM3 has been predicted to be a potential biomarker for disease progression in MM.This study provides proof of concept that a range of biologically significant proteins of interest can be reliably detected in the saliva of MM and MGUS patients. The observation of differential expression of FABP5 between MGUS and MM identified these as candidate proteins relevant to malignant transformation of MGUS to symptomatic MM. The demonstration of decreased abundance of FABP5 after achieving remission indicates a correlation with tumour burden. This opens the opportunity to explore candidate salivary biomarkers for use in the clinic for disease monitoring and Minimal Residual Disease (MRD) assessment. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Saliva – A Promising Tool for Diagnosing Oral Diseases

This review will present updates on the genome, transcriptome, proteome, metabolome, exosome, and microbiome of saliva and the wide range of biomarkers found within these salivary components. We will explore the effectiveness and potential of salivary diagnostics on specific diseases: dental caries and demineralization diseases, periodontal diseases and peri-implantitis, oral cancers, and Sjogren’s syndrome. Recent studies have shown the feasibility of saliva as a diagnostic tool, in addition to the emergence of many novel salivary biomarkers. Unfortunately, many of these studies do not explore further into the outcomes of patient-oriented health and do not demonstrate reliability in diverse patient populations. Salivary diagnostics is an emerging field that uses saliva, for its non-invasive, fast, and cost-effective collection properties, as a diagnostic tool. In the near future, we expect that salivary diagnostics will benefit from technological advances and further studies to be used as a routine chair-side test included in a comprehensive diagnostic and risk assessment tool.

Changes in salivary analytes in canine parvovirus: A high-resolution quantitative proteomic study.

The present study evaluated the changes in salivary proteome in parvoviral enteritis (PVE) in dogs through a high-throughput quantitative proteomic analysis. Saliva samples from healthy dogs and dogs with severe parvovirosis that survived or perished due to the disease were analysed and compared by Tandem Mass Tags (TMT) analysis. Proteomic analysis quantified 1516 peptides, and 287 (corresponding to 190 proteins) showed significantly different abundances between studied groups. Ten proteins were observed to change significantly between dogs that survived or perished due to PVE. Bioinformatics' analysis revealed that saliva reflects the involvement of different pathways in PVE such as catalytic activity and binding, and indicates antimicrobial humoral response as a pathway with a major role in the development of the disease. These results indicate that saliva proteins reflect physiopathological changes that occur in PVE and could be a potential source of biomarkers for this disease.