Oral Fluid-Based Molecular Diagnostics

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 November 2016) | Viewed by 77879

Special Issue Editors


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Guest Editor
1. Center for Oral and Head/Neck Oncology Research, School of Dentistry, University of California at Los Angeles, Los Angeles, CA 90095, USA
2. Section of Biosystems and Function, School of Dentistry, University of California at Los Angeles, Los Angeles, CA 90095, USA
Interests: oral cancer; salivary diagnostics; salivaomics; liquid biopsy; early detection

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Guest Editor
Head Molecular Diagnostics, Department of Health & Environment, Austria Institute of Technology, Donau-City-Strasse 1, 1220 Wien, Austria

Special Issue Information

Dear Colleagues,

The holy grail of diagnostics is a perfect performance and non-invasiveness. Saliva is non-invasive so ideally fulfills the secondary goal. Emerging genomic and proteomic technologies and omic-based biomarker development has credentialed saliva as a scientific biofluid for translational and clinical utilities. Combining this with advancements in detection technologies, to enable single copy molecular targets and/or biomarkers, will allow for the maturation of this clinical path to impact clinical and diagnostic practice. The realization of the first goal of perfect diagnostic performance is beginning to be envisioned. A key to full credentialing of saliva diagnostics is to demonstrate that saliva constituents can be developed, conclusively validated and regulatory-approved. The era of precision and personalized medicine is upon us and the emerging landscape of saliva-based diagnostics is timely and impactful.

Prof. Dr. David Wong
Dr. Martin Weber
Guest Editor

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Keywords

  • oral fluid-based molecular diagnostics
  • saliva diagnostics
  • non-invasive
  • genomic and proteomic technologies
  • omic-based biomarker development

Published Papers (8 papers)

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Research

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1528 KiB  
Article
Salivary Immune and Metabolic Marker Analysis (SIMMA): A Diagnostic Test to Predict Caries Risk
by Alex Mira, Alejandro Artacho, Anny Camelo-Castillo, Sandra Garcia-Esteban and Aurea Simon-Soro
Diagnostics 2017, 7(3), 38; https://doi.org/10.3390/diagnostics7030038 - 27 Jun 2017
Cited by 12 | Viewed by 8680
Abstract
By using ELISA and colorimetric tests, we have measured 25 compounds in individuals with and without dental caries at different time points of dental biofilm formation and time of the day. We find that some compounds appear to be affected by circadian rhythms, [...] Read more.
By using ELISA and colorimetric tests, we have measured 25 compounds in individuals with and without dental caries at different time points of dental biofilm formation and time of the day. We find that some compounds appear to be affected by circadian rhythms, others by dental plaque maturity, and others show constant values during a 24 h period. Using univariate analysis and cross-validation techniques, we have selected six components measured at specific time points that maximize the diagnostic separation of health and disease conditions. Two out of the six selected compounds are related to immune competence, another two to the adhesion capacity of micro-organisms, and another two to acid production or pH buffering. We conclude that, in order to design a robust caries risk test, the time of saliva sampling must be standardized and biomarkers from different categories must be included. The preliminary data shown in this paper provide a proof of principle of a caries risk test based on risk-associated categories. Thus, the test will provide not only a general caries risk assessment, but also the likely biological origin of that risk, namely: immune imbalance, and/or a tendency to adhesion of cariogenic organisms, and/or a lack of acid buffering. When tested longitudinally and validated in larger cohorts, this could open the possibility to develop preventive and personalized treatments. Full article
(This article belongs to the Special Issue Oral Fluid-Based Molecular Diagnostics)
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472 KiB  
Article
A Pilot Study into the Association between Oral Health Status and Human Papillomavirus—16 Infection
by Charles Xiaohang Sun, Nigel Bennett, Peter Tran, Kai Dun Tang, Yenkai Lim, Ian Frazer, Lakshman Samaranayake and Chamindie Punyadeera
Diagnostics 2017, 7(1), 11; https://doi.org/10.3390/diagnostics7010011 - 01 Mar 2017
Cited by 44 | Viewed by 7409
Abstract
Background: Over the next 20 years, oropharyngeal cancers (OPC) will represent the majority of head and neck cancers (HNCs) in the United States. It is estimated that human papillomavirus (HPV) may account for as much as 70% to 80% of OPCs in North [...] Read more.
Background: Over the next 20 years, oropharyngeal cancers (OPC) will represent the majority of head and neck cancers (HNCs) in the United States. It is estimated that human papillomavirus (HPV) may account for as much as 70% to 80% of OPCs in North America and in certain parts of Europe. It is hence crucial to understand the disease risk factors and natural history of oral HPV infections. We hypothesized that poor oral health (by measures such as poor oral hygiene and periodontal disease) leads to a higher degree of oral HPV-16 infections within a patient cohort from a dental school clinic. This study aims to test this hypothesis and gauge possible disease associations before larger scale studies. Subjects and Methods: 223 participants were recruited in this study from the University of Queensland Dental School clinic. Clinical oral health parameters (such as oral hygiene measures and periodontal disease measurements) have been examined and determined by dental professionals. We have collected oral rinse samples from these volunteers. Results: 10 (4.5%) out of 223 participants were found to have HPV-16 DNA in their oral rinse samples using NB2 endpoint PCR and Sanger sequencing. Within the HPV-16 DNA positive subjects, 7 (70%) and 3 (30%) were associated with poor oral hygiene and periodontal disease, respectively. Conclusion: Our results show a trend towards a positive correlation between oral HPV-16 infection and poor clinical oral health status. Full article
(This article belongs to the Special Issue Oral Fluid-Based Molecular Diagnostics)
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1773 KiB  
Article
Gingival Crevicular Fluid as a Novel Potential Source of Biomarkers Distinguishes Pubertal from Post-Pubertal Subjects
by Xi Wen, Yan Gu and Feng Chen
Diagnostics 2016, 6(4), 41; https://doi.org/10.3390/diagnostics6040041 - 17 Nov 2016
Cited by 4 | Viewed by 5834
Abstract
Detection of pubertal growth peak is vital in orthodontic treatment timing and planning. Gingival crevicular fluid (GCF) contains abundant proteins from different sources and has been proven to be an ideal source of biomarkers. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) is an [...] Read more.
Detection of pubertal growth peak is vital in orthodontic treatment timing and planning. Gingival crevicular fluid (GCF) contains abundant proteins from different sources and has been proven to be an ideal source of biomarkers. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) is an advanced technique that can detect low-molecular-weight peptides with high sensitivity and resolution. The aim of this research was to identify novel candidate biomarkers in GCF to help the diagnosis of pubertal growth peak by MALDI-TOF/MS. Results showed that the peak intensities of six peptides were significantly different between two groups: 1660.2 Da, 1783.0 Da, 2912.5 Da, 4178.6 Da, 5064.9 Da, and 6108.9 Da and are considered to be potential candidate biomarkers to identify pubertal growth peak. Further studies are needed to identify sequence information of these candidate biomarkers. Full article
(This article belongs to the Special Issue Oral Fluid-Based Molecular Diagnostics)
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188 KiB  
Article
The Effect of Exercise on Salivary Viscosity
by Antoon J. M. Ligtenberg, Erwin H. S. Liem, Henk S. Brand and Enno C. I. Veerman
Diagnostics 2016, 6(4), 40; https://doi.org/10.3390/diagnostics6040040 - 16 Nov 2016
Cited by 19 | Viewed by 7773
Abstract
A common experience after exercise is the presence of a thick and sticky saliva layer on the oral surfaces, which causes a feeling of a dry mouth. Since the salivary mucin MUC5B is responsible for the visco-elastic behavior of saliva, in the present [...] Read more.
A common experience after exercise is the presence of a thick and sticky saliva layer on the oral surfaces, which causes a feeling of a dry mouth. Since the salivary mucin MUC5B is responsible for the visco-elastic behavior of saliva, in the present study we explored the effect of exercise on both the salivary viscosity and the secretion of MUC5B in saliva. Twenty healthy dental students performed an aerobic exercise by cycling for 15 min on cycle-ergometers at a heart rate of 130–140 beats per minute. Saliva was collected at three time points: before exercise, immediately after exercise and after 30 min recovery. Salivary flow rate, viscosity, amylase activity, total protein, carbohydrate and MUC5B concentration were determined. Salivary flow rate, protein and amylase did not change significantly. Immediately after exercise, the salivary viscosity and carbohydrate concentration were significantly higher than at baseline and after 30 min recovery. Immediately after exercise, the MUC5B concentration was significantly higher than after 30 min recovery. It is concluded that the presence of thick saliva after exercise is at least partially due to an increased secretion of MUC5B. Full article
(This article belongs to the Special Issue Oral Fluid-Based Molecular Diagnostics)
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Article
Endogenous Intoxication and Saliva Lipid Peroxidation in Patients with Lung Cancer
by Lyudmila V. Bel’skaya, Victor K. Kosenok and Gilbert Massard
Diagnostics 2016, 6(4), 39; https://doi.org/10.3390/diagnostics6040039 - 16 Nov 2016
Cited by 18 | Viewed by 7125
Abstract
This research was aimed at a search for regularities in changes to parameters of endogenous intoxication and saliva lipid peroxidation in patients with lung cancer, non-malignant lung diseases, and apparently healthy people. All patients went through saliva sampling at an amount of 1 [...] Read more.
This research was aimed at a search for regularities in changes to parameters of endogenous intoxication and saliva lipid peroxidation in patients with lung cancer, non-malignant lung diseases, and apparently healthy people. All patients went through saliva sampling at an amount of 1 mL. A concentration of malondialdehyde (MDA) was measured according to a reaction with thiobarbituric acid, and a level of middle molecules (MM) was measured with UV spectroscopy at 254 and 280 nm, while the content of lipid peroxidation products was measured according to a degree of heptane extract light absorption at wavelengths of 220, 232, 278, and 400 nm. It has been revealed that in the context of lung cancer, the level of diene conjugates decreases, increasing the level of triene conjugates, Schiff’s bases, and MM. As a tumor grows, there is a decrease in the level of lipid peroxidation primary products and an increase in endotoxemia phenomena. The process is more apparent when going from local to locally advanced disease states. The nature of the MDA change is nonlinearly associated with tumor progression. The findings might be used to optimize traditional aids of diagnostics, in disease state forecasting, in treatment monitoring, etc. Full article
(This article belongs to the Special Issue Oral Fluid-Based Molecular Diagnostics)
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Review

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2127 KiB  
Review
Salivary IL-8, IL-6 and TNF-α as Potential Diagnostic Biomarkers for Oral Cancer
by Haafsa Arshad Sahibzada, Zohaib Khurshid, Rabia Sannam Khan, Mustafa Naseem, Khalid Mahmood Siddique, Maria Mali and Muhammad Sohail Zafar
Diagnostics 2017, 7(2), 21; https://doi.org/10.3390/diagnostics7020021 - 09 Apr 2017
Cited by 117 | Viewed by 13451
Abstract
Saliva has been useful as a liquid biopsy for the diagnosis of various oral or systemic diseases, and oral squamous cell carcinoma (OSCC) is no exception. While its early detection and prevention is important, salivary cytokines expression, specifically of Interleukin-8 (IL-8), Interleukin-6 (IL-6) [...] Read more.
Saliva has been useful as a liquid biopsy for the diagnosis of various oral or systemic diseases, and oral squamous cell carcinoma (OSCC) is no exception. While its early detection and prevention is important, salivary cytokines expression, specifically of Interleukin-8 (IL-8), Interleukin-6 (IL-6) and Tumor necrosis factor (TNF-α), does contribute to the pathogenesis of cancer and these cytokines serve as potential biomarkers. Their excessive production plays a role in cancer progression and establishment of angiogenesis. However, other inflammatory or immunological conditions may affect the levels of cytokines in saliva. This article reviews the expression of levels of specific cytokines i.e., IL-8, IL-6 and TNF-α, their signaling pathways in the development of oral cancer, and how they are essential for the diagnosis of OSCC and updates related to it. Apart from serum, the saliva-based test can be a cost-effective tool in the follow-up and diagnosis of OSCC. Moreover, large-scale investigations are still needed for the validation of salivary cytokines. Full article
(This article belongs to the Special Issue Oral Fluid-Based Molecular Diagnostics)
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1929 KiB  
Review
Salivary Diagnostics—Point-of-Care diagnostics of MMP-8 in dentistry and medicine
by Nilminie Rathnayake, Dirk-Rolf Gieselmann, Anna Maria Heikkinen, Taina Tervahartiala and Timo Sorsa
Diagnostics 2017, 7(1), 7; https://doi.org/10.3390/diagnostics7010007 - 20 Jan 2017
Cited by 64 | Viewed by 18917
Abstract
Human saliva is an easily accessible biological fluid and contains a variety of disease-related biomarkers, which makes it a potential diagnostic medium. The clinical use of salivary/oral fluid biomarkers to identify oral and systemic conditions requires the development of non-invasive screening and diagnostic [...] Read more.
Human saliva is an easily accessible biological fluid and contains a variety of disease-related biomarkers, which makes it a potential diagnostic medium. The clinical use of salivary/oral fluid biomarkers to identify oral and systemic conditions requires the development of non-invasive screening and diagnostic technologies, and is among the main goals of oral fluid researchers. The analysis of the disease-specific oral and systemic biomarkers in saliva and oral fluids (i.e., mouth-rinse, gingival crevicular fluid (GCF) and peri-implantitis sulcular fluid (PISF)) is demanding. Several factors influence their expression and release; these factors include the intracellular location, the molecular size and the flow characteristics of the biological fluid. The type of saliva/oral fluid utilized for the diagnostics affects the analysis. High sensitivity together with sophisticated methods and techniques are essential to get a useful outcome. We describe here a recently developed mouth-rinse that is practical, convenient and inexpensive, as well as PISF chair-side/point of care (PoC) lateral-flow active matrix metalloproteinase (aMMP-8) immunoassays to detect, predict and monitor the course and treatment of periodontitis and peri-implantitis. Full article
(This article belongs to the Special Issue Oral Fluid-Based Molecular Diagnostics)
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233 KiB  
Review
Oral Biofluid Biomarker Research: Current Status and Emerging Frontiers
by Austin Wang, Chris P. Wang, Michael Tu and David T.W. Wong
Diagnostics 2016, 6(4), 45; https://doi.org/10.3390/diagnostics6040045 - 17 Dec 2016
Cited by 46 | Viewed by 7739
Abstract
Salivary diagnostics is a rapidly advancing field that offers clinicians and patients the potential of rapid, noninvasive diagnostics with excellent accuracy. In order for the complete realization of the potential of saliva, however, extensive profiling of constituents must be conducted and diagnostic biomarkers [...] Read more.
Salivary diagnostics is a rapidly advancing field that offers clinicians and patients the potential of rapid, noninvasive diagnostics with excellent accuracy. In order for the complete realization of the potential of saliva, however, extensive profiling of constituents must be conducted and diagnostic biomarkers must be thoroughly validated. This article briefly overviews the process of conducting a study of salivary biomarkers in a patient cohort and highlights the studies that have been conducted on different classes of molecules in the saliva. Emerging frontiers in salivary diagnostics research that may significantly advance the field will also be highlighted. Full article
(This article belongs to the Special Issue Oral Fluid-Based Molecular Diagnostics)
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