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Human Saliva as a Source of Biomarkers for Oral Diseases
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Human Saliva as a Source of Biomarkers for Oral Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 23408

Special Issue Editors

Prof. Dr. Alberto Spisni

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Parma, Parma, Italy
Interests: NMR; circular dichroism of proteins and peptides; protein and peptide structure; structural biology; metabolomics clinical applications; blood storage and transfusion
Prof. Dr. Marco Meleti

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy
Interests: Salivary Biomarkers; Salivary glands; Laser Therapy; Oral pigmented lesions; Potential malignant diseases
Prof. Dr. Thelma Pertinhez

E-Mail Website
Guest Editor
Università degli Studi di Parma, Parma, Italy

Special Issue Information

Dear colleagues,

In the past 10 years, we faced a tremendous surge in studies on salivary biomarkers, including gene transcripts, proteins, and metabolites. The use of “omics” sciences to study saliva has led to the definition of a new field of oral sciences: “salivomics”. The focus is to interpret the molecular content of each type of saliva in view of the physiological and pathological processes occurring in salivary glands, oral cavity, and the whole body.

The identification of specific salivary molecules associated with physiological or pathological states has promoted the development of novel and non-invasive diagnostic tools for oral health evaluation and biomarker identification.

Topics of the present Special Issue include, but are not limited to:

  • Salivary biomarkers for dental and periodontal diagnosis
  • Salivary biomarkers and oral mucosal diseases
  • Salivary biomarkers and salivary gland diseases
  • Salivary biomarkers and jawbones diseases

The purpose of this Special Issue is to present the state-of the-art of the multifaceted aspects of saliva. Thus, we invite scientists to send original research articles as well as review articles to further stimulate the efforts necessary to comprehend the heterogeneity of the molecules present in saliva, the biochemical mechanisms they reflect, and the diagnostic potentiality they hide.

Prof. Dr. Alberto Spisni
Prof. Dr. Marco Meleti
Prof. Dr. Thelma Pertinhez
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • saliva subtype composition
  • diagnosis
  • biomarkers
  • metabolites
  • proteins
  • miRNA

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Published Papers (5 papers)

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Research

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15 pages, 2383 KiB  
Article
Salivary Outer Membrane Vesicles and DNA Methylation of Small Extracellular Vesicles as Biomarkers for Periodontal Status: A Pilot Study
by Pingping Han, Peter Mark Bartold, Carlos Salomon and Sašo Ivanovski
Int. J. Mol. Sci. 2021, 22(5), 2423; https://doi.org/10.3390/ijms22052423 - 28 Feb 2021
Cited by 50 | Viewed by 4594
Abstract
Periodontitis is an inflammatory disease, associated with a microbial dysbiosis. Early detection using salivary small extracellular vesicles (sEVs) biomarkers may facilitate timely prevention. sEVs derived from different species (i.e., humans, bacteria) are expected to circulate in saliva. This pilot study recruited 22 participants [...] Read more.
Periodontitis is an inflammatory disease, associated with a microbial dysbiosis. Early detection using salivary small extracellular vesicles (sEVs) biomarkers may facilitate timely prevention. sEVs derived from different species (i.e., humans, bacteria) are expected to circulate in saliva. This pilot study recruited 22 participants (seven periodontal healthy, seven gingivitis and eight periodontitis) and salivary sEVs were isolated using the size-exclusion chromatography (SEC) method. The healthy, gingivitis and periodontitis groups were compared in terms of salivary sEVs in the CD9+ sEV subpopulation, Gram-negative bacteria-enriched lipopolysaccharide (LPS+) outer membrane vesicles (OMVs) and global DNA methylation pattern of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and N6-Methyladenosine (m6dA). It was found that LPS+ OMVs, global 5mC methylation and four periodontal pathogens (T. denticola, E. corrodens, P. gingivalis and F. nucleatum) that secreted OMVs were significantly increased in periodontitis sEVs compared to those from healthy groups. These differences were more pronounced in sEVs than the whole saliva and were more superior in distinguishing periodontitis than gingivitis, in comparison to healthy patients. Of note, global 5mC hypermethylation in salivary sEVs can distinguish periodontitis patients from both healthy controls and gingivitis patients with high sensitivity and specificity (AUC = 1). The research findings suggest that assessing global sEV methylation may be a useful biomarker for periodontitis. Full article
(This article belongs to the Special Issue Human Saliva as a Source of Biomarkers for Oral Diseases)
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Review

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14 pages, 586 KiB  
Review
Salivary Biomarkers in Patients with Sjögren’s Syndrome—A Systematic Review
by Ju-Yang Jung, Ji-Won Kim, Hyoun-Ah Kim and Chang-Hee Suh
Int. J. Mol. Sci. 2021, 22(23), 12903; https://doi.org/10.3390/ijms222312903 - 29 Nov 2021
Cited by 20 | Viewed by 4410
Abstract
Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by dry mouth and dry eyes, with lymphocytic infiltration of the exocrine glands. Saliva is becoming a useful tool to determine the clinical and pathological characteristics of SS because the collection method is easy [...] Read more.
Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by dry mouth and dry eyes, with lymphocytic infiltration of the exocrine glands. Saliva is becoming a useful tool to determine the clinical and pathological characteristics of SS because the collection method is easy and non-invasive. Since 1900, salivary proteomic analysis has been performed continuously using a variety of optimized analytical methods. Many studies have identified distinct characteristics of salivary proteins in patients with primary SS, and the changes were related to chronic inflammation and overproduction of immunoglobulins or downregulated secretory function. Several proteomic studies using whole or parotid saliva have evaluated whether several salivary proteins can be used to discriminate SS, including salivary β2-microglobulin, calprotectin, carbonic anhydrase VI, neutrophil gelatinase-associated lipocalin, sialic acid-binding immunoglobulin-like lectin-5, and tripartite motif-containing protein 29. In addition, salivary proinflammatory cytokine levels have been reported to be increased in patients with SS. Although these candidate salivary proteins have exhibited considerable differences in patients with SS, more data are needed to confirm their role as biomarkers. Moreover, the identification of salivary characteristics that can accurately reflect disease activity, predict treatment response and prognosis, and diagnose SS is anticipated. Full article
(This article belongs to the Special Issue Human Saliva as a Source of Biomarkers for Oral Diseases)
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13 pages, 326 KiB  
Review
Role of Salivary MicroRNA and Cytokines in the Diagnosis and Prognosis of Oral Squamous Cell Carcinoma
by Francisco Javier Manzano-Moreno, Victor J. Costela-Ruiz, Enrique García-Recio, Maria Victoria Olmedo-Gaya, Concepción Ruiz and Candelaria Reyes-Botella
Int. J. Mol. Sci. 2021, 22(22), 12215; https://doi.org/10.3390/ijms222212215 - 11 Nov 2021
Cited by 33 | Viewed by 3530
Abstract
Oral squamous cell carcinoma (OSCC) is the most prevalent oral malignant tumor worldwide. An early diagnosis can have a major positive impact on its prognosis. Human saliva contains cytokines, DNA and RNA molecules, circulating cells, and derivatives of tissues and extracellular vesicles, among [...] Read more.
Oral squamous cell carcinoma (OSCC) is the most prevalent oral malignant tumor worldwide. An early diagnosis can have a major positive impact on its prognosis. Human saliva contains cytokines, DNA and RNA molecules, circulating cells, and derivatives of tissues and extracellular vesicles, among other factors that can serve as biomarkers. Hence, the analysis of saliva may provide useful information for the early diagnosis of OSCC for its prognosis. The objective of this review was to determine the potential usefulness of salivary biomarkers (cytokines and microRNA) to diagnose OSCC and improve its prognosis. A combination of salivary miRNA and proteomic data could allow a definitive and early diagnosis to be obtained. However, there remains a need to optimize and standardize the protocols used to quantify miRNAs. Full article
(This article belongs to the Special Issue Human Saliva as a Source of Biomarkers for Oral Diseases)
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14 pages, 948 KiB  
Review
Salivary Cytokines as Biomarkers for Oral Squamous Cell Carcinoma: A Systematic Review
by Elena Ferrari, Margherita E. Pezzi, Diana Cassi, Thelma A. Pertinhez, Alberto Spisni and Marco Meleti
Int. J. Mol. Sci. 2021, 22(13), 6795; https://doi.org/10.3390/ijms22136795 - 24 Jun 2021
Cited by 48 | Viewed by 4138
Abstract
The prognosis of patients with oral squamous carcinoma (OSCC) largely depends on the stage at diagnosis, the 5-year survival rate being approximately 30% for advanced tumors. Early diagnosis, including the detection of lesions at risk for malignant transformation, is crucial for limiting the [...] Read more.
The prognosis of patients with oral squamous carcinoma (OSCC) largely depends on the stage at diagnosis, the 5-year survival rate being approximately 30% for advanced tumors. Early diagnosis, including the detection of lesions at risk for malignant transformation, is crucial for limiting the need for extensive surgery and for improving disease-free survival. Saliva has gained popularity as a readily available source of biomarkers (including cytokines) useful for diagnosing specific oral and systemic conditions. Particularly, the close interaction between oral dysplastic/neoplastic cells and saliva makes such fluid an ideal candidate for the development of non-invasive and highly accurate diagnostic tests. The present review has been designed to answer the question: “Is there evidence to support the role of specific salivary cytokines in the diagnosis of OSCC?” We retrieved 27 observational studies satisfying the inclusion and exclusion criteria. Among the most frequent cytokines investigated as candidates for OSCC biomarkers, IL-6, IL-8, TNF-α are present at higher concentration in the saliva of OSCC patients than in healthy controls and may therefore serve as basis for the development of rapid tests for early diagnosis of oral cancer. Full article
(This article belongs to the Special Issue Human Saliva as a Source of Biomarkers for Oral Diseases)
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9 pages, 509 KiB  
Review
A Bioinformatics Systems Biology Analysis of the Current Oral Proteomic Biomarkers and Implications for Diagnosis and Treatment of External Root Resorption
by Mahmoud Mona, Zunnaira Abbasi, Firas Kobeissy, Abdulrahman Chahbandar and Roberta Pileggi
Int. J. Mol. Sci. 2021, 22(6), 3181; https://doi.org/10.3390/ijms22063181 - 20 Mar 2021
Cited by 9 | Viewed by 5722
Abstract
External root resorption (ERR) is a silent destructive phenomenon detrimental to dental health. ERR may have multiple etiologies such as infection, inflammation, traumatic injuries, pressure, mechanical stimulations, neoplastic conditions, systemic disorders, or idiopathic causes. Often, if undiagnosed and untreated, ERR can lead to [...] Read more.
External root resorption (ERR) is a silent destructive phenomenon detrimental to dental health. ERR may have multiple etiologies such as infection, inflammation, traumatic injuries, pressure, mechanical stimulations, neoplastic conditions, systemic disorders, or idiopathic causes. Often, if undiagnosed and untreated, ERR can lead to the loss of the tooth or multiple teeth. Traditionally, clinicians have relied on radiographs and cone beam computed tomography (CBCT) images for the diagnosis of ERR; however, these techniques are not often precise or definitive and may require exposure of patients to more ionizing radiation than necessary. To overcome these shortcomings, there is an immense need to develop non-invasive approaches such as biomarker screening methods for rapid and precise diagnosis for ERR. In this review, we performed a literature survey for potential salivary or gingival crevicular fluid (GCF) proteomic biomarkers associated with ERR and analyzed the potential pathways leading to ERR. To the best of our knowledge, this is the first proteomics biomarker survey that connects ERR to body biofluids which represents a novel approach to diagnose and even monitor treatment progress for ERR. Full article
(This article belongs to the Special Issue Human Saliva as a Source of Biomarkers for Oral Diseases)
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